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Li Y, Han J, Gong R, Liu Y, Zhou Y, Gong T, Wang B, Zhang L, Li S, Chen J. Protective effects of Paeonia suffruticosa callus extract in skin through anti-inflammation and repair UVB-induced damage. Int J Cosmet Sci 2025. [PMID: 40079176 DOI: 10.1111/ics.13055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 01/24/2025] [Accepted: 01/30/2025] [Indexed: 03/14/2025]
Abstract
OBJECTIVE The study investigated effects of peony callus extracts (PCE) on the protective efficacy against Ultraviolet B (UVB)-induced photoageing, using in vitro and in vivo studies. The research focused on PCE's ability to protect against inflammatory factors, DNA damage and accumulation of senescent cells, along with the evaluation of the extract's potential anti-photoageing benefits to skin. METHODS Human keratinocyte cell line (HaCaT cells), mast cells and fibroblasts were used to evaluate the role of PCE in anti-photoageing. The expression of genes of interleukin-1α (IL-1α), IL-6 and transient receptor potential vanilloid 1 (TRPV1) were tested in HaCaT cells. The histamine contents in mast cells were tested to evaluate the effect of PCE on soothing skin. Additionally, the repairment of PCE on DNA damage stimulated by UVB using comet assay was evaluated. In fibroblasts, the gene expression of matrix metalloproteinases (MMPs) and the activity of β-galactosidase were tested. In vivo test, 13 healthy volunteers were enrolled to apply a formula with 1% PCE to assess the variation in inner skin collagen contents. RESULTS The callus from an ancient and rare variety of tree peony (Paeoniaceae family) was successfully induced, and its ingredients were extracted. The PCE could significantly downregulate inflammation factors such as IL-1α, IL-6 and TRPV1 in HaCaT cells, and MMPs in fibroblasts which could cause the collagen degradation induced by UVB. Meanwhile, UVB-induced DNA damage was alleviated by PCE. The analysis of histamine content in mast cells revealed that PCE effectively alleviated skin sensitivity. Furthermore, the clinical trials validated a significant increase in total collagen content in vivo, following 28 days of continuous application of a cosmetic formulation containing 1% PCE measured by Raman confocal spectroscopy technology. CONCLUSION The PCE could downregulate the gene expression of inflammatory factors, indicating the ability of DNA repair. The number of senescent cells was also decreased after UVB stimulation. Furthermore, the results of in vivo study showed that PCE was an ideal cosmetic ingredient for promoting collagen levels.
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Affiliation(s)
- Yufan Li
- State Key Laboratory of Protein and Plant Gene Research, School of Advanced Agriculture Sciences and School of Life Sciences, Peking University, Beijing, China
- Hangzhou Shiguang Xinya Biotechnology Co., Ltd., Hangzhou, China
| | | | | | - Yuankun Liu
- Hangzhou Shiguang Xinya Biotechnology Co., Ltd., Hangzhou, China
| | - Yu Zhou
- Hangzhou Shiguang Xinya Biotechnology Co., Ltd., Hangzhou, China
| | | | - Bin Wang
- MCL Skincare Ltd., Hangzhou, China
| | - Laidi Zhang
- Hangzhou Shiguang Xinya Biotechnology Co., Ltd., Hangzhou, China
| | - Shuodan Li
- Hangzhou Shiguang Xinya Biotechnology Co., Ltd., Hangzhou, China
| | - Jiayue Chen
- Hangzhou Shiguang Xinya Biotechnology Co., Ltd., Hangzhou, China
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Juodžiukynienė N, Lasienė K, Savickienė N, Aniulienė A. Mast Cell Density in Squamous Cell Carcinoma of Skin in Dogs and Cats. Animals (Basel) 2025; 15:316. [PMID: 39943085 PMCID: PMC11816034 DOI: 10.3390/ani15030316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Revised: 01/12/2025] [Accepted: 01/17/2025] [Indexed: 02/16/2025] Open
Abstract
The purpose of the present study was to evaluate mast cell density in squamous cell carcinoma tissues of dogs and cats to assess species differences. Skin squamous cell carcinoma tissues from dogs (n = 15: n = 10 from body sites and n = 5 nail bed specimens) and cats (n = 15, n = 10 from ears and n = 5 nasal planum specimens) were examined. Intratumoral mast cell density (IMCD), peritumoral mast cell density (PMCD) and total mast cells density (TMCD) as a sum of IMCD and PMCD were calculated from Giemsa-stained slides at high magnification in 1 mm2 using an Olympus microscope (Olympus BX41, Tokyo, Japan) equipped with a digital Olympus DP72 image camera and CellSensDimension software V1.16). Both intratumoral and peritumoral tissues of the squa.mous cell carcinoma were divided into two categories: (1) loose, well-vascularized, rich in lymphocytes and plasmocytes, macrophages and neutrophils; and (2) fibrous, with few or no lymphocytes, plasmocytes, macrophages and neutrophils (the presence of neutrophils can be associated with actinic keratosis, mechanical irritation of the tumor in some anatomical areas during scratching with teeth, but, in general, neutrophils are associated with more invasive squamous cell carcinoma). In cats, a markedly higher total number of mast cells was found, and the number was also higher in intratumoral and peritumoral tissues. A similar tendency was found in both dogs and cats-a markedly higher number of mastocytes was found in both peritumoral and intratumoral loose, well-vascularized connective tissue. Conversely, lower numbers of mast cells were found in both intratumoral and peritumoral compact fibrous tissue in both animal species.
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Affiliation(s)
- Nomeda Juodžiukynienė
- Department of Veterinary Pathobiology, Faculty of Veterinary Medicine, Veterinary Academy, Lithuanian University of Health Sciences, A.Mickevičius Str. 9, LT-44307 Kaunas, Lithuania;
| | - Kristina Lasienė
- Deparment of Histology and Embryology, Faculty of Medicine, Medical Academy, Lithuanian University of Health Sciences, A.Mickevičius Str. 9, LT-44307 Kaunas, Lithuania;
| | - Nijolė Savickienė
- Department of Pharmacognosy, Faculty of Pharmacy, Medical Academy, Lithuanian University of Health Sciences, A.Mickevičius Str. 9, LT-44307 Kaunas, Lithuania;
| | - Albina Aniulienė
- Department of Veterinary Pathobiology, Faculty of Veterinary Medicine, Veterinary Academy, Lithuanian University of Health Sciences, A.Mickevičius Str. 9, LT-44307 Kaunas, Lithuania;
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Korhonen J, Siiskonen H, Haimakainen S, Harvima RJ, Harvima IT. Expression of mast cell tryptase and immunoglobulin E is increased in cutaneous photodamage: implications for carcinogenesis. J DERMATOL TREAT 2024; 35:2307488. [PMID: 38291602 DOI: 10.1080/09546634.2024.2307488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 01/15/2024] [Indexed: 02/01/2024]
Abstract
Purpose: Mast cells, their serine proteinase tryptase, and immunoglobulin E (IgE) can be involved in cutaneous carcinogenesis.Materials and methods: To study the association of tryptase+ and IgE+ cells with photodamage and skin cancers 385 adult patients (201 males, 184 females, 75 with immunosuppression) at risk of any type of skin cancer were examined. Skin biopsies were taken from the sun-protected medial arm and from the photodamaged dorsal forearm skin followed by immunohistochemical staining for tryptase and IgE.Results: The results show that tryptase+ and IgE+ cells are significantly higher in number in the photodamaged than sun-protected skin, both in immunocompetent and -compromised subjects, and there is a strong correlation between tryptase+ and IgE+ cells. The numbers of forearm tryptase+ and especially IgE+ cells associated significantly with the forearm photodamage severity. In the logistic regression analysis, the forearm to upper arm ratio of IgE+ cells produced a univariate odds ratio of 1.521 (p = .010) and a multivariate one of 3.875 (p = .047) for the history of squamous cell carcinoma. The serum level of total IgE correlated significantly to the IgE to tryptase ratio in both skin sites.Conclusions: Therefore, IgE+ mast cells participate in photodamage and carcinogenesis, though it is unclear whether they are tumor-protective or -causative.
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Affiliation(s)
- Jenni Korhonen
- Department of Dermatology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
| | - Hanna Siiskonen
- Department of Dermatology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
| | - Salla Haimakainen
- Department of Dermatology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
| | - Rauno J Harvima
- Department of Dermatology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
| | - Ilkka T Harvima
- Department of Dermatology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
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Kaszuba A, Sławińska M, Żółkiewicz J, Sobjanek M, Nowicki RJ, Lange M. Mastocytosis and Skin Cancer: The Current State of Knowledge. Int J Mol Sci 2023; 24:9840. [PMID: 37372988 DOI: 10.3390/ijms24129840] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 05/26/2023] [Accepted: 05/29/2023] [Indexed: 06/29/2023] Open
Abstract
Mastocytosis is a heterogeneous group of diseases associated with excessive proliferation and accumulation of mast cells in different organs. Recent studies have demonstrated that patients suffering from mastocytosis face an increased risk of melanoma and non-melanoma skin cancer. The cause of this has not yet been clearly identified. In the literature, the potential influence of several factors has been suggested, including genetic background, the role of cytokines produced by mast cells, iatrogenic and hormonal factors. The article summarizes the current state of knowledge regarding the epidemiology, pathogenesis, diagnosis, and management of skin neoplasia in mastocytosis patients.
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Affiliation(s)
- Agnieszka Kaszuba
- Department of Dermatology, Venereology and Allergology, Medical University of Gdańsk, Smoluchowskiego Street 17, 80-214 Gdańsk, Poland
| | - Martyna Sławińska
- Department of Dermatology, Venereology and Allergology, Medical University of Gdańsk, Smoluchowskiego Street 17, 80-214 Gdańsk, Poland
| | - Jakub Żółkiewicz
- Department of Dermatology, Venereology and Allergology, Medical University of Gdańsk, Smoluchowskiego Street 17, 80-214 Gdańsk, Poland
| | - Michał Sobjanek
- Department of Dermatology, Venereology and Allergology, Medical University of Gdańsk, Smoluchowskiego Street 17, 80-214 Gdańsk, Poland
| | - Roman J Nowicki
- Department of Dermatology, Venereology and Allergology, Medical University of Gdańsk, Smoluchowskiego Street 17, 80-214 Gdańsk, Poland
| | - Magdalena Lange
- Department of Dermatology, Venereology and Allergology, Medical University of Gdańsk, Smoluchowskiego Street 17, 80-214 Gdańsk, Poland
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Wong HY, Lee RC, Chong S, Kapadia S, Freeman M, Murigneux V, Brown S, Soyer HP, Roy E, Khosrotehrani K. Epidermal mutation accumulation in photodamaged skin is associated with skin cancer burden and can be targeted through ablative therapy. SCIENCE ADVANCES 2023; 9:eadf2384. [PMID: 37163607 PMCID: PMC10171798 DOI: 10.1126/sciadv.adf2384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/12/2023]
Abstract
The main carcinogen for keratinocyte skin cancers (KCs) such as basal and squamous cell carcinomas is ultraviolet (UV) radiation. There is growing evidence that accumulation of mutations and clonal expansion play a key role in KC development. The relationship between UV exposure, epidermal mutation load, and KCs remains unclear. Here, we examined the mutation load in both murine (n = 23) and human (n = 37) epidermal samples. Epidermal mutations accumulated in a UV dose-dependent manner, and this mutation load correlated with the KC burden. Epidermal ablation (either mechanical or laser induced), followed by spontaneous healing from underlying epithelial adnexae reduced the mutation load markedly in both mouse (n = 8) and human (n = 6) clinical trials. In a model of UV-induced basal cell carcinoma, epidermal ablation reduced incident lesions by >80% (n = 5). Overall, our findings suggest that mutation burden is strongly associated with KC burden and represents a target to prevent subsequent KCs.
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Affiliation(s)
- Ho Yi Wong
- Dermatology Research Centre, Experimental Dermatology Group, Frazer Institute, The University of Queensland, Brisbane, Australia
- Dermatology Research Centre, Frazer Institute, The University of Queensland, Brisbane, Australia
| | - Ruby C Lee
- Dermatology Research Centre, Experimental Dermatology Group, Frazer Institute, The University of Queensland, Brisbane, Australia
- Dermatology Research Centre, Frazer Institute, The University of Queensland, Brisbane, Australia
- Department of Dermatology, Princess Alexandra Hospital, Brisbane, Australia
| | - Sharene Chong
- Dermatology Research Centre, Experimental Dermatology Group, Frazer Institute, The University of Queensland, Brisbane, Australia
- Dermatology Research Centre, Frazer Institute, The University of Queensland, Brisbane, Australia
- Department of Dermatology, Princess Alexandra Hospital, Brisbane, Australia
| | - Stuti Kapadia
- Dermatology Research Centre, Experimental Dermatology Group, Frazer Institute, The University of Queensland, Brisbane, Australia
- Dermatology Research Centre, Frazer Institute, The University of Queensland, Brisbane, Australia
| | - Michael Freeman
- Department of Dermatology, Princess Alexandra Hospital, Brisbane, Australia
| | - Valentine Murigneux
- QCIF Facility for Advanced Bioinformatics, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia
| | - Susan Brown
- Dermatology Research Centre, Experimental Dermatology Group, Frazer Institute, The University of Queensland, Brisbane, Australia
- Department of Dermatology, Princess Alexandra Hospital, Brisbane, Australia
| | - H Peter Soyer
- Dermatology Research Centre, Frazer Institute, The University of Queensland, Brisbane, Australia
- Department of Dermatology, Princess Alexandra Hospital, Brisbane, Australia
| | - Edwige Roy
- Dermatology Research Centre, Experimental Dermatology Group, Frazer Institute, The University of Queensland, Brisbane, Australia
- Dermatology Research Centre, Frazer Institute, The University of Queensland, Brisbane, Australia
| | - Kiarash Khosrotehrani
- Dermatology Research Centre, Experimental Dermatology Group, Frazer Institute, The University of Queensland, Brisbane, Australia
- Dermatology Research Centre, Frazer Institute, The University of Queensland, Brisbane, Australia
- Department of Dermatology, Princess Alexandra Hospital, Brisbane, Australia
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Ligeralde-Bascones KI, Gulmatico-Flores Z, Lim-Bueser HG, Espinoza-Thaebtharm A, Rescober-Valencia MC, Aguila KP, Anupol EBJ, Balete SL, Barcelona MV, Castro VCS, Fineza-Dela Cruz AMB, Lansangan PP, Manrique AMB, Olitoquit KD, Ortiz ACG, Palisoc ED, Santos DGV, See MRV, Sy AJF, Sy GC, Tana MG, Tayag JJS, Teo HMT. Diagnosis and management of basal cell carcinoma: interdisciplinary consensus statements of Jose R. Reyes Memorial Medical Center, a Department of Health Tertiary Hospital in Manila, Philippines. Int J Dermatol 2022; 62:812-821. [PMID: 36562635 DOI: 10.1111/ijd.16555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 11/19/2022] [Accepted: 11/30/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Basal cell carcinoma (BCC) is the most common cutaneous malignancy. Multiple risk factors are associated in the development of BCC, with ultraviolet light and genetics playing major roles. AIMS The departments of dermatology, medical oncology, ophthalmology, otorhinolaryngology, head and neck surgery, plastic surgery, and radiation oncology of the Jose R. Reyes Memorial Medical Center, Manila, Philippines, have convened and formulated consensus statements on the diagnosis and management of BCC patients seen in the institution. CONCLUSION The summary of the recommendations is: (1) Surgery is the treatment of choice for BCC. The range of margins (2-4 mm) depends on the type of BCC. (2) Mohs micrographic surgery (MMS) is indicated for high risk BCC. (3) Topical treatment with imiquimod or 5-flourouracil (5-FU) may be used for superficial BCC. (4) Destructive methods (cryotherapy, curettage and electrodessication, photodynamic therapy) may be used for low risk BCC. (5) Medical and/or radiation therapy is advised for cases where surgery is contraindicated or tumor is not amenable to surgery. Metastasis of this malignancy is rare. Follow-up, which may continue up until 2 years, is recommended for high risk BCC.
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Affiliation(s)
| | | | | | | | | | - Konrad P Aguila
- Department of Otorhinolaryngology, Head and Neck Surgery, Jose R. Reyes Memorial Medical Center, Manila, Philippines
| | - Elisa B J Anupol
- Department of Dermatology, Jose R. Reyes Memorial Medical Center, Manila, Philippines
| | - Solidad L Balete
- Department of Internal Medicine, Section of Medical Oncology, Jose R. Reyes Memorial Medical Center, Manila, Philippines
| | - Marc V Barcelona
- Department of Radiation Oncology, Jose R. Reyes Memorial Medical Center, Manila, Philippines
| | - Vhon C S Castro
- Department of Internal Medicine, Section of Medical Oncology, Jose R. Reyes Memorial Medical Center, Manila, Philippines
| | | | - Patrick P Lansangan
- Department of Dermatology, Jose R. Reyes Memorial Medical Center, Manila, Philippines
| | - Aldric M B Manrique
- Department of Radiation Oncology, Jose R. Reyes Memorial Medical Center, Manila, Philippines
| | - Katrina D Olitoquit
- Department of Dermatology, Jose R. Reyes Memorial Medical Center, Manila, Philippines
| | - Anthony C G Ortiz
- Department of Ophthalmology, Jose R. Reyes Memorial Medical Center, Manila, Philippines
| | - Erwin D Palisoc
- Department of Ophthalmology, Jose R. Reyes Memorial Medical Center, Manila, Philippines
| | - Danziel G V Santos
- Department of Ophthalmology, Jose R. Reyes Memorial Medical Center, Manila, Philippines
| | - Melissa R V See
- Department of Dermatology, Jose R. Reyes Memorial Medical Center, Manila, Philippines
| | - Austin J F Sy
- Department of Otorhinolaryngology, Head and Neck Surgery, Jose R. Reyes Memorial Medical Center, Manila, Philippines
| | - Gerald C Sy
- Department of Surgery, Section of Plastic Surgery, Jose R. Reyes Memorial Medical Center, Manila, Philippines
| | - Mobbydick G Tana
- Department of Dermatology, Jose R. Reyes Memorial Medical Center, Manila, Philippines
| | - Joseph J S Tayag
- Department of Dermatology, Jose R. Reyes Memorial Medical Center, Manila, Philippines
| | - Honeylen M T Teo
- Department of Ophthalmology, Jose R. Reyes Memorial Medical Center, Manila, Philippines
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7
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Roy E, Wong HY, Villani R, Rouille T, Salik B, Sim SL, Murigneux V, Stark MS, Fink JL, Soyer HP, Walker G, Lyons JG, Saunders N, Khosrotehrani K. Regional Variation in Epidermal Susceptibility to UV-Induced Carcinogenesis Reflects Proliferative Activity of Epidermal Progenitors. Cell Rep 2021; 31:107702. [PMID: 32492418 DOI: 10.1016/j.celrep.2020.107702] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 03/12/2020] [Accepted: 05/06/2020] [Indexed: 11/29/2022] Open
Abstract
To better understand the influence of ultraviolet (UV) irradiation on the initial steps of skin carcinogenesis, we examine patches of labeled keratinocytes as a proxy for clones in the interfollicular epidermis (IFE) and measure their size variation upon UVB irradiation. Multicolor lineage tracing reveals that in chronically irradiated skin, patches near hair follicles (HFs) increase in size, whereas those far from follicles do not change. This is explained by proliferation of basal epidermal cells within 60 μm of HF openings. Upon interruption of UVB, patch size near HFs regresses significantly. These anatomical differences in proliferative behavior have significant consequences for the cell of origin of basal cell carcinomas (BCCs). Indeed, a UV-inducible murine BCC model shows that BCC patches are more frequent, larger, and more invasive near HFs. These findings have major implications for the prevention of field cancerization in the epidermis.
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Affiliation(s)
- Edwige Roy
- The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD 4102, Australia
| | - Ho Yi Wong
- The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD 4102, Australia
| | - Rehan Villani
- The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD 4102, Australia
| | - Thomas Rouille
- UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD 4029, Australia
| | - Basit Salik
- UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD 4029, Australia
| | - Seen Ling Sim
- The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD 4102, Australia
| | - Valentine Murigneux
- The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD 4102, Australia
| | - Mitchell S Stark
- The University of Queensland Diamantina Institute, The University of Queensland, Dermatology Research Centre, Brisbane, QLD 4102, Australia
| | - J Lynn Fink
- The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD 4102, Australia
| | - H Peter Soyer
- The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD 4102, Australia; The University of Queensland Diamantina Institute, The University of Queensland, Dermatology Research Centre, Brisbane, QLD 4102, Australia
| | - Graeme Walker
- QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
| | - J Guy Lyons
- Discipline of Dermatology, Bosch Institute, Charles Perkins Centre, The University of Sydney, NSW 2006, Australia
| | - Nicholas Saunders
- The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD 4102, Australia
| | - Kiarash Khosrotehrani
- The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD 4102, Australia; UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD 4029, Australia.
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8
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Garg C, Sharma H, Garg M. Skin photo-protection with phytochemicals against photo-oxidative stress, photo-carcinogenesis, signal transduction pathways and extracellular matrix remodeling-An overview. Ageing Res Rev 2020; 62:101127. [PMID: 32721499 DOI: 10.1016/j.arr.2020.101127] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Revised: 07/04/2020] [Accepted: 07/15/2020] [Indexed: 12/19/2022]
Abstract
Excessive exposure of skin to UV radiation triggers the generation of oxidative stress, inflammation, immunosuppression, apoptosis, matrix-metalloproteases production, and DNA mutations leading to the onset of photo ageing and photo-carcinogenesis. At the molecular level, these changes occur via activation of several protein kinases as well as transcription pathways, formation of reactive oxygen species, and release of cytokines, interleukins and prostaglandins together. Current therapies available on the market only provide limited solutions and exhibit several side effects. The present paper provides insight into scientific studies that have elucidated the positive role of phytochemicals in counteracting the UV-induced depletion of antioxidant enzymes, increased lipid peroxidation, inflammation, DNA mutations, increased senescence, dysfunctional apoptosis and immune suppression. The contribution of phytochemicals to the downregulation of expression of oxidative-stress sensitive transcription factors (Nrf2, NF-Kb, AP-1 and p53) and protein kinases (MSK, ERK, JNK, p38 MAPK, p90RSK2 and CaMKs) involved in inflammation, apoptosis, immune suppression, extracellular matrix remodelling, senescence, photo ageing and photo-carcinogenesis, is also discussed. Conclusively, several phytochemicals hold potential for the development of a viable solution against UV irradiation-mediated photo ageing, photo-carcinogenesis and related manifestations.
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9
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Bachtiar M, Jin Y, Wang J, Tan TW, Chong SS, Ban KHK, Lee CGL. Architecture of population-differentiated polymorphisms in the human genome. PLoS One 2019; 14:e0224089. [PMID: 31622447 PMCID: PMC6797171 DOI: 10.1371/journal.pone.0224089] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Accepted: 10/04/2019] [Indexed: 12/25/2022] Open
Abstract
Population variation in disease and other phenotype are partly attributed to single nucleotide polymorphisms (SNPs) in the human genome. Due to selection pressure, two individuals from the same ancestral population have more genetic similarity compared to individuals from further geographic regions. Here, we elucidated the genomic population differentiation pattern, by interrogating >22,000,000 SNPs. Majority of population-differentiated (pd) SNPs (~95%), including the potentially functional (pf) (~84%) subset reside in non-genic regions, compared to the proportion of all SNPs (58%) found in non-genic regions. This suggests that differences between populations are more likely due to differences in gene regulation rather than protein function. Actin Cytoskeleton, Axonal Guidance and Protein Kinase A signaling pathways are enriched with genes carrying at least three pdSNPs (enriched pdGenes), while Antigen Presentation, Hepatic Fibrosis and Huntington Disease Signalling pathways are over-represented by enriched pf-pdGenes. An inverse correlation between chromosome size and the proportion of pd-/pf-pdSNPs was observed. Smaller chromosomes have relatively more of such SNPs including genes carrying these SNPs. Genes associated with common diseases and enriched with these pd-/pfpdSNPs are localized to 11 different chromosomes, with immune-related disease pd/pf-pdGenes mainly residing in chromosome 6 while neurological disease pd/pf-pdGenes residing in smaller chromosomes including chromosome 21/22. The associated diseases were reported to show population differences in incidence, severity and/or etiology. In summary, this study highlights the non-sporadic nature of population differentiation footprint in the human genome, which can potentially lead to the identification of genomic regions that play roles in the manifestation of phenotypic differences, including in disease predisposition and drug response.
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Affiliation(s)
- Maulana Bachtiar
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Cellular & Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, Singapore
| | - Yu Jin
- Division of Cellular & Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, Singapore
| | - Jingbo Wang
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Tin Wee Tan
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- National Supercomputing Centre Singapore, Singapore
| | - Samuel S. Chong
- Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Kenneth H. K. Ban
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Caroline G. L. Lee
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Cellular & Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, Singapore
- Cancer & Stem Cell Biology Programme, Duke-NUS Graduate Medical School, Singapore
- * E-mail:
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10
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Estrella-Parra EA, Espinosa-González AM, García-Bores AM, Zamora-Salas SX, Benítez-Flores JC, González-Valle MR, Hernández-Delgado CT, Peñalosa-Castro I, Avila-Acevedo JG. Flavonol glycosides in Dyssodia tagetiflora and its temporal variation, chemoprotective and ameliorating activities. Food Chem Toxicol 2018; 124:411-422. [PMID: 30576709 DOI: 10.1016/j.fct.2018.12.024] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 12/12/2018] [Accepted: 12/17/2018] [Indexed: 11/25/2022]
Abstract
Dyssodia tagetiflora is known as 'Tzaracata' and 'flor de muerto'. Recently, D. tagetiflora has been reported to have antioxidant activities in its polar extracts as well as insecticidal activities. Hyperoside (1), avicularin (2) and avicularin acetate (3) have been isolated previously. However, the temporary variation in glycoside flavonoids biosynthesis, as well as antibacterial and chemoprotective activities, have not been reported. The amount of 1, 2 and 3 in the different collections was characterized by HPLC-MS. Two new C-glycosides were characterized, quercetin-4'-methyl ether 6-C glucoside (A1) and quercetin-4'-methyl ether 8-C glucoside (A2), as well as [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxochromen-3-yl]3,4,5-trihydroxyoxane-2,6-dicarboxylate (A3). This is the first report of the presence of C-C flavonoid glycosides compounds in the genus Dyssodia. Hyperoside was the majority compound at all collections. The methanolic extracts of August 2016 and October 2017 were active against Micrococcus luteus and Bacillus subtillis. The methanolic extract has chemoprotective effects because, when applied topically in SKH-1 mice, it decreases the severity of epidermal damage induced by acute exposure to ultraviolet radiation. In addition, cutaneous photocarcinogenesis was decreased in mice treated with the extract. The methanolic extract of D. tagetiflora has chemoprotective properties by decreasing the damage caused by acute and chronic exposure to UV in mice.
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Affiliation(s)
- E A Estrella-Parra
- Laboratorio de Fitoquímica, UBIPRO, FES-Iztacala, Unidad Nacional Autónoma de México, Av. de los Barrios No.1, Los Reyes Iztacala, Tlalnepantla, 54090, Estado de México, México
| | - A M Espinosa-González
- Laboratorio de Fitoquímica, UBIPRO, FES-Iztacala, Unidad Nacional Autónoma de México, Av. de los Barrios No.1, Los Reyes Iztacala, Tlalnepantla, 54090, Estado de México, México
| | - A M García-Bores
- Laboratorio de Fitoquímica, UBIPRO, FES-Iztacala, Unidad Nacional Autónoma de México, Av. de los Barrios No.1, Los Reyes Iztacala, Tlalnepantla, 54090, Estado de México, México
| | - S X Zamora-Salas
- Laboratorio de Fitoquímica, UBIPRO, FES-Iztacala, Unidad Nacional Autónoma de México, Av. de los Barrios No.1, Los Reyes Iztacala, Tlalnepantla, 54090, Estado de México, México
| | - J C Benítez-Flores
- Laboratorio de Histología, UMF, FES-Iztacala, Universidad Nacional Autónoma de México, Av. de los Barrios No.1, Los Reyes Iztacala, Tlalnepantla, 54090, Edo. de México, México
| | - M R González-Valle
- Laboratorio de Histología, UMF, FES-Iztacala, Universidad Nacional Autónoma de México, Av. de los Barrios No.1, Los Reyes Iztacala, Tlalnepantla, 54090, Edo. de México, México
| | - C T Hernández-Delgado
- Laboratorio de Farmacognosia, UBIPRO, Universidad Nacional Autónoma de México, Av. de los Barrios No.1, Los Reyes Iztacala, Tlalnepantla, 54090, Estado de México, México
| | - I Peñalosa-Castro
- Laboratorio de Fitoquímica, UBIPRO, FES-Iztacala, Unidad Nacional Autónoma de México, Av. de los Barrios No.1, Los Reyes Iztacala, Tlalnepantla, 54090, Estado de México, México
| | - J G Avila-Acevedo
- Laboratorio de Fitoquímica, UBIPRO, FES-Iztacala, Unidad Nacional Autónoma de México, Av. de los Barrios No.1, Los Reyes Iztacala, Tlalnepantla, 54090, Estado de México, México.
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11
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Saito P, Melo CPB, Martinez RM, Fattori V, Cezar TLC, Pinto IC, Bussmann AJC, Vignoli JA, Georgetti SR, Baracat MM, Verri WA, Casagrande R. The Lipid Mediator Resolvin D1 Reduces the Skin Inflammation and Oxidative Stress Induced by UV Irradiation in Hairless Mice. Front Pharmacol 2018; 9:1242. [PMID: 30429790 PMCID: PMC6220064 DOI: 10.3389/fphar.2018.01242] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Accepted: 10/12/2018] [Indexed: 12/19/2022] Open
Abstract
UV irradiation-induced oxidative stress and inflammation contribute to the development of skin diseases. Therefore, targeting oxidative stress and inflammation might contribute to reduce skin diseases. Resolvin D1 (RvD1) is a bioactive metabolite generated during inflammation to actively orchestrate the resolution of inflammation. However, the therapeutic potential of RvD1 in UVB skin inflammation remains undetermined, which was, therefore, the aim of the present study. The intraperitoneal treatment with RvD1 (3-100 ng/mouse) reduced UVB irradiation-induced skin edema, myeloperoxidase activity, matrix metalloproteinase 9 activity, and reduced glutathione depletion with consistent effects observed with the dose of 30 ng/mouse, which was selected to the following experiments. RvD1 inhibited UVB reduction of catalase activity, and hydroperoxide formation, superoxide anion production, and gp91phox mRNA expression. RvD1 also increased the Nrf2 and its downstream targets NQO1 and HO-1 mRNA expression. Regarding cytokines, RvD1 inhibited UVB-induced production of IL-1β, IL-6, IL-33, TNF-α, TGF-β, and IL-10. These immuno-biochemical alterations by RvD1 treatment had as consequence the reduction of UVB-induced epidermal thickness, sunburn and mast cell counts, and collagen degradation. Therefore, RvD1 inhibited UVB-induced skin oxidative stress and inflammation, rendering this resolving lipid mediator as a promising therapeutic agent.
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Affiliation(s)
- Priscila Saito
- Laboratory of Oxidative Stress and Inflammation, Department of Pharmaceutical Sciences, Londrina State University, Londrina, Brazil
| | - Cristina P. B. Melo
- Laboratory of Oxidative Stress and Inflammation, Department of Pharmaceutical Sciences, Londrina State University, Londrina, Brazil
| | - Renata M. Martinez
- Laboratory of Oxidative Stress and Inflammation, Department of Pharmaceutical Sciences, Londrina State University, Londrina, Brazil
- Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Brazil
| | - Victor Fattori
- Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Brazil
| | - Talita L. C. Cezar
- Laboratory of Oxidative Stress and Inflammation, Department of Pharmaceutical Sciences, Londrina State University, Londrina, Brazil
| | - Ingrid C. Pinto
- Laboratory of Oxidative Stress and Inflammation, Department of Pharmaceutical Sciences, Londrina State University, Londrina, Brazil
| | - Allan J. C. Bussmann
- Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Brazil
| | - Josiane A. Vignoli
- Department of Biochemistry and Biotechnology, Londrina State University, Londrina, Brazil
| | - Sandra R. Georgetti
- Laboratory of Oxidative Stress and Inflammation, Department of Pharmaceutical Sciences, Londrina State University, Londrina, Brazil
| | - Marcela M. Baracat
- Laboratory of Oxidative Stress and Inflammation, Department of Pharmaceutical Sciences, Londrina State University, Londrina, Brazil
| | - Waldiceu A. Verri
- Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Brazil
| | - Rubia Casagrande
- Laboratory of Oxidative Stress and Inflammation, Department of Pharmaceutical Sciences, Londrina State University, Londrina, Brazil
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12
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Grammatophyllum speciosum Ethanolic Extract Promotes Wound Healing in Human Primary Fibroblast Cells. Int J Cell Biol 2018; 2018:7836869. [PMID: 30420887 PMCID: PMC6215563 DOI: 10.1155/2018/7836869] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Revised: 10/05/2018] [Accepted: 10/09/2018] [Indexed: 12/20/2022] Open
Abstract
Grammatophyllum speciosum is a plant in Orchidaceae family which contains a variety of phytochemical compounds that might be beneficial for medicinal use. This study aimed to evaluate the activity of pseudobulb of G. speciosum extract (GSE) in wound healing processes in human primary fibroblast cells along with in vitro antioxidant activity and total phenolic content of GSE. Scratch wound healing assay indicated that GSE was capable of increasing migration rate after 6 and 9 hours of treatment. Besides, the extract was able to scavenge DPPH, ABTS, and superoxide anion radicals indicating the antioxidative property of GSE. This study suggested a novel role of the of pseudobulb extract of G. speciosum as a wound healing enhancer. The results from this study might be beneficial for the development of further novel active compounds for skin wound healing.
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13
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Patra V, Laoubi L, Nicolas JF, Vocanson M, Wolf P. A Perspective on the Interplay of Ultraviolet-Radiation, Skin Microbiome and Skin Resident Memory TCRαβ+ Cells. Front Med (Lausanne) 2018; 5:166. [PMID: 29900173 PMCID: PMC5988872 DOI: 10.3389/fmed.2018.00166] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Accepted: 05/11/2018] [Indexed: 12/21/2022] Open
Abstract
The human skin is known to be inhabited by diverse microbes, including bacteria, fungi, viruses, archaea, and mites. This microbiome exerts a protective role against infections by promoting immune development and inhibiting pathogenic microbes to colonize skin. One of the factors having an intense effect on the skin and its resident microbes is ultraviolet-radiation (UV-R). UV-R can promote or inhibit the growth of microbes on the skin and modulate the immune system which can be either favorable or harmful. Among potential UV-R targets, skin resident memory T cells (TRM) stand as well positioned immune cells at the forefront within the skin. Both CD4+ or CD8+ αβ TRM cells residing permanently in peripheral tissues have been shown to play prominent roles in providing accelerated and long-lived specific immunity, tissue homeostasis, wound repair. Nevertheless, their response upon UV-R exposure or signals from microbiome are poorly understood compared to resident TCRγδ cells. Skin TRM survive for long periods of time and are exposed to innumerable antigens during lifetime. The interplay of TRM with skin residing microbes may be crucial in pathophysiology of various diseases including psoriasis, atopic dermatitis and polymorphic light eruption. In this article, we share our perspective about how UV-R may directly shape the persistence, phenotype, specificity, and function of skin TRM; and moreover, whether UV-R alters barrier function, leading to microbial-specific skin TRM, disrupting the healthy balance between skin microbiome and skin immune cells, and resulting in chronic inflammation and diseased skin.
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Affiliation(s)
- VijayKumar Patra
- Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale, U1111, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique, UMR5308, Ecole Normale Supérieure de Lyon, Université de Lyon, Lyon, France.,Center for Medical Research, Medical University of Graz, Graz, Austria.,Research Unit for Photodermatology, Department of Dermatology, Medical University of Graz, Graz, Austria
| | - Léo Laoubi
- Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale, U1111, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique, UMR5308, Ecole Normale Supérieure de Lyon, Université de Lyon, Lyon, France
| | - Jean-François Nicolas
- Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale, U1111, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique, UMR5308, Ecole Normale Supérieure de Lyon, Université de Lyon, Lyon, France.,Allergy and Clinical Immunology Department, Lyon Sud University Hospital, Pierre-Bénite, France
| | - Marc Vocanson
- Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale, U1111, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique, UMR5308, Ecole Normale Supérieure de Lyon, Université de Lyon, Lyon, France
| | - Peter Wolf
- Research Unit for Photodermatology, Department of Dermatology, Medical University of Graz, Graz, Austria
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Kim YM, Kim J, Lee JY, Kim M, Kim H, Jung K, Eo S, Ahn M, Ahn K. Impact of solar ultraviolet radiation on atopic dermatitis symptoms in young children: A longitudinal study. Pediatr Allergy Immunol 2017. [PMID: 28631848 DOI: 10.1111/pai.12746] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND There are controversial data about the effects of sun exposure on atopic dermatitis (AD). We evaluated the association between solar ultraviolet radiation (UVR) exposure and AD symptoms in children. METHODS Eighty-two children under 6 years (48 boys and 34 girls) with AD living in Seoul, Korea, were enrolled and followed for 12 months between September 2013 and August 2014. Daily symptoms were recorded to describe the degree of itching, sleep disturbance, erythema, dryness, oozing, and edema. We assessed solar UVR by measuring radiation heat flux over the 290-400 nm wavelength range using thermopiles. A generalized linear mixed model and a generalized additive mixed model were used to evaluate the effects of UVR exposure on AD symptoms after adjusting for age, sex, outdoor temperature, outdoor humidity, and ambient air pollution. RESULTS Symptom records of 12 915 person-days were analyzed. UVR showed a significantly positive relationship with AD symptoms. Over the study period, an increase in UVR by 10 W/cm2 was associated with a 1.46% increase in AD symptoms (95% CI: 0.85-2.07) on the exposure day. An increase in the 6-day average level of UVR of the previous 5 days and the current day by 10 W/cm2 was associated with a 3.58% (95% CI: 2.60-4.56) increase in AD symptoms. UVR exposure significantly increased AD symptoms in autumn, but decreased them in winter. CONCLUSIONS Atopic dermatitis symptoms in children are likely to be affected by exposure to solar UVR with a cumulative effect, and this effect is different according to season.
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Affiliation(s)
- Young-Min Kim
- The Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.,The Environmental Health Center for Atopic Diseases, Samsung Medical Center, Seoul, Korea
| | - Jihyun Kim
- The Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.,The Environmental Health Center for Atopic Diseases, Samsung Medical Center, Seoul, Korea
| | - Ji Young Lee
- The Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Minji Kim
- The Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyunmi Kim
- The Environmental Health Center for Atopic Diseases, Samsung Medical Center, Seoul, Korea
| | - Kwon Jung
- The Seoul Research Institute of Public Health and Environment, Gwacheon, Korea
| | - Soomi Eo
- The Seoul Research Institute of Public Health and Environment, Gwacheon, Korea
| | - Mijin Ahn
- The Seoul Research Institute of Public Health and Environment, Gwacheon, Korea
| | - Kangmo Ahn
- The Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.,The Environmental Health Center for Atopic Diseases, Samsung Medical Center, Seoul, Korea
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15
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Lupu M, Caruntu A, Caruntu C, Papagheorghe LML, Ilie MA, Voiculescu V, Boda D, Constantin C, Tanase C, Sifaki M, Drakoulis N, Mamoulakis C, Tzanakakis G, Neagu M, Spandidos DA, Izotov BN, Tsatsakis AM. Neuroendocrine factors: The missing link in non‑melanoma skin cancer (Review). Oncol Rep 2017; 38:1327-1340. [PMID: 28713981 PMCID: PMC5549028 DOI: 10.3892/or.2017.5817] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Accepted: 06/29/2017] [Indexed: 02/06/2023] Open
Abstract
Non‑melanoma skin cancer (NMSC) is the most common form of cancer worldwide, comprising 95% of all cutaneous malignancies and approximately 40% of all cancers. In spite of intensive efforts aimed towards awareness campaigns and sun‑protective measures, epidemiological data indicate an increase in the incidence of NMSC. This category of skin cancers has many common environmental triggers. Arising primarily on sun‑exposed skin, it has been shown that ultraviolet radiation is, in the majority of cases, the main trigger involved in the pathogenesis of NMSC. Aside from the well‑known etiopathogenic factors, studies have indicated that several neuroactive factors are involved in the carcinogenesis of two of the most common types of NMSC, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), with the exception of penile SCC, for which a paucity of specific data on their pathogenic role exists. The complex interaction between the peripheral nervous system and target cells in the skin appears to be mediated by locally released neuroendocrine factors, such as catecholamines, substance P, calcitonin gene‑related peptide and somatostatin, as well as neurohormones, such as proopiomelanocortin and its derived peptides, α‑melanocyte‑stimulating hormone and adrenocorticotropin. All these factors have been, at least at some point, a subject of debate regarding their precise role in the pathogenesis of NMSC. There is also a significant body of evidence indicating that psychological stress is a crucial impact factor influencing the course of skin cancers, including SCC and BCC. Numerous studies have suggested that neuroendocrine factor dysregulation, as observed in stress reactions, may be involved in tumorigenesis, accelerating the development and progression, and suppressing the regression of NMSC. Further studies are required in order to elucidate the exact mechanisms through which neuroactive molecules promote or inhibit cutaneous carcinogenesis, as this could lead to the development of more sophisticated and tailored treatment protocols, as well as open new perspectives in skin cancer research.
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Affiliation(s)
- Mihai Lupu
- Department of Dermatology, MEDAS Medical Center, 030442 Bucharest, Romania
| | - Ana Caruntu
- Department of Oral and Maxillofacial Surgery, ‘Carol Davila’ Central Military Emergency Hospital, 010825 Bucharest, Romania
- ‘Titu Maiorescu’ University, Faculty of Medicine, 031593 Bucharest, Romania
| | - Constantin Caruntu
- Department of Physiology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Dermatology, ‘Prof. N. Paulescu’ National Institute of Diabetes, Nutrition and Metabolic Diseases, 011233 Bucharest, Romania
| | | | - Mihaela Adriana Ilie
- Dermatology Research Laboratory, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Vlad Voiculescu
- Department of Dermatology and Allergology, Elias Emergency University Hospital, 011461 Bucharest, Romania
| | - Daniel Boda
- Dermatology Research Laboratory, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Carolina Constantin
- ‘Victor Babes’ National Institute of Pathology, 050096 Bucharest, Romania
- Colentina University Hospital, 020125 Bucharest, Romania
| | - Cristiana Tanase
- ‘Titu Maiorescu’ University, Faculty of Medicine, 031593 Bucharest, Romania
- ‘Victor Babes’ National Institute of Pathology, 050096 Bucharest, Romania
| | - Maria Sifaki
- Laboratory of Toxicology, Faculty of Medicine, University of Crete, 71003 Heraklion, Greece
| | - Nikolaos Drakoulis
- Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15771 Athens, Greece
| | - Charalampos Mamoulakis
- Department of Urology, University General Hospital of Heraklion, University of Crete Medical School, 71003 Heraklion, Greece
| | - George Tzanakakis
- Laboratory of Anatomy-Histology-Embryology, School of Medicine, University of Crete, 71003 Heraklion, Greece
| | - Monica Neagu
- ‘Victor Babes’ National Institute of Pathology, 050096 Bucharest, Romania
- Colentina University Hospital, 020125 Bucharest, Romania
| | - Demetrios A. Spandidos
- Laboratory of Clinical Virology, Medical School, University of Crete, 71003 Heraklion, Greece
| | - Boris N. Izotov
- Department of Analytical Toxicology, Pharmaceutical Chemistry and Pharmacognosy, Sechenov University, 119991 Moscow, Russia
| | - Aristides M. Tsatsakis
- Laboratory of Toxicology, Faculty of Medicine, University of Crete, 71003 Heraklion, Greece
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16
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Rajabi P, Bagheri A, Hani M. Intratumoral and Peritumoral Mast Cells in Malignant Melanoma: An Immunohistochemical Study. Adv Biomed Res 2017; 6:39. [PMID: 28503494 PMCID: PMC5414406 DOI: 10.4103/2277-9175.204592] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND The aim of the current study was to determine mast cell infiltration in malignant melanoma by immunohistochemistry method and its relationship with some of the cancer prognostic factors, including age, sex, and depth of the tumor. MATERIALS AND METHODS In this retrospective analytic cross-sectional study, paraffin-embedded tissue blocks of patients with cutaneous malignant melanoma who had undergone excisional biopsy were studied. Mast cells count in studied cases in different stages of the tumor depth was evaluated by mast cell tryptase immunohistochemistry method. Mast cells infiltration was evaluated both inside the tumor and peritumoral area. Tumor infiltrating lymphocytes (TILs) was also determined. Distribution of intratumoral and peritumoral mast cells and TILs was compared in different stages tof tumor depth. RESULTS In this study, 51 cases with melanoma were studied. Mean ± standard deviation (SD) of intratumoral mast cells in stages 1, 2, and 3 was 9.4 ± 4.2, 10.8 ± 5.1, and 2.1 ± 2.3, respectively (P = 0.000). Mean ± SD of peritumoral mast cells in stages 1, 2 and 3 was 13.4 ± 2.4, 16.6 ± 2.4 and 8.2 ± 4.6, respectively (P = 0.000). There was a significant direct relationship between depth of the tumor and TIL (P = 0.000) and distribution of intratumoral (P = 0.000) and peritumoral mast cells (P = 0.000). CONCLUSION Lower distribution of intratumoral and peritumoral mast cells and TILs in higher stages of tumor depth in malignant melanoma suggests a possible inhibitory effect of infiltrating mast cells and lymphocytes on the progression of this tumor.
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Affiliation(s)
- Parvin Rajabi
- Department of Pathology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Azam Bagheri
- Department of Pathology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohssen Hani
- Department of Pathology, Isfahan University of Medical Sciences, Isfahan, Iran
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17
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UV-Induced Molecular Signaling Differences in Melanoma and Non-melanoma Skin Cancer. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 996:27-40. [PMID: 29124688 DOI: 10.1007/978-3-319-56017-5_3] [Citation(s) in RCA: 90] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
There are three major types of skin cancer: melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCC and SCC are often referred to as non-melanoma skin cancer (NMSC). NMSCs are relatively non-lethal and curable by surgery, hence are not reportable in most cancer registries all over the world. Melanoma is the deadliest skin cancer. Its incidence rate (case number) is about 1/10th of that for NMSC, yet its death toll is ~8 fold higher than NMSC.Melanomas arise from melanocytes which are normally located on the basement membrane with dendrites extending into the epidermal keratinocytes. A major known function of melanocytes is to produce pigments which are enclosed by lipid membrane (termed melanosomes) and distribute them into keratinocytes, thus give different shade of skin colors. BCCs arise from basal cells, which are a layer of cells located at the deepest part of epidermis. Basal cells are recently considered to be skin stem cells as they are constantly proliferating and generating keratinocytes which are continuously pushed to the surface and eventually become a dead layer of stratum corneum. Squamous cells are the keratinocytes which resembles fish scale shape, ie, those initiated from basal cells and differentiated into squamous cells. Both basal cells and squamous cells belong to keratinocytes, therefore sometimes BCC and SCC are termed keratinocyte cancer.These three types of cancer share many characteristics, yet they are very different from etiology to progression. One shared characteristic of skin cancer is that, according to the current views, they all are caused by solar or artificial ultraviolet radiation (UVR). UVA and UVB from solar UVR are the major UV bands reaching the earth surface. Both UV types cause DNA damage and immune suppression which play crucial roles in skin carcinogenesis. UVB can be directly absorbed by DNA molecules and thus causes UV-signature DNA damages; UVA, on the other hand, may function through inducing cellular ROS which then causes oxidative DNA damages [1-4]. This chapter will discuss the molecular signaling differences of UVR in melanoma and NMSC.
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18
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Patra V, Byrne SN, Wolf P. The Skin Microbiome: Is It Affected by UV-induced Immune Suppression? Front Microbiol 2016; 7:1235. [PMID: 27559331 PMCID: PMC4979252 DOI: 10.3389/fmicb.2016.01235] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Accepted: 07/25/2016] [Indexed: 12/12/2022] Open
Abstract
Human skin apart from functioning as a physical barricade to stop the entry of pathogens, also hosts innumerable commensal organisms. The skin cells and the immune system constantly interact with microbes, to maintain cutaneous homeostasis, despite the challenges offered by various environmental factors. A major environmental factor affecting the skin is ultraviolet radiation (UV-R) from sunlight. UV-R is well known to modulate the immune system, which can be both beneficial and deleterious. By targeting the cells and molecules within skin, UV-R can trigger the production and release of antimicrobial peptides, affect the innate immune system and ultimately suppress the adaptive cellular immune response. This can contribute to skin carcinogenesis and the promotion of infectious agents such as herpes simplex virus and possibly others. On the other hand, a UV-established immunosuppressive environment may protect against the induction of immunologically mediated skin diseases including some of photodermatoses such as polymorphic light eruption. In this article, we share our perspective about the possibility that UV-induced immune suppression may alter the landscape of the skin’s microbiome and its components. Alternatively, or in concert with this, direct UV-induced DNA and membrane damage to the microbiome may result in pathogen associated molecular patterns (PAMPs) that interfere with UV-induced immune suppression.
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Affiliation(s)
- VijayKumar Patra
- Research Unit for Photodermatology, Department of Dermatology, Medical University of GrazGraz, Austria; Center for Medical Research, Medical University of GrazGraz, Austria
| | - Scott N Byrne
- Cellular Photoimmunology Group, Infectious Diseases and Immunology, Sydney Medical School, The Charles Perkins Center Hub at The University of Sydney, Sydney NSW, Australia
| | - Peter Wolf
- Research Unit for Photodermatology, Department of Dermatology, Medical University of Graz Graz, Austria
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Brazzelli V, Grassi S, Merante S, Grasso V, Ciccocioppo R, Bossi G, Borroni G. Narrow-band UVB phototherapy and psoralen-ultraviolet A photochemotherapy in the treatment of cutaneous mastocytosis: a study in 20 patients. PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE 2016; 32:238-246. [PMID: 27353865 DOI: 10.1111/phpp.12248] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 06/20/2016] [Indexed: 12/16/2022]
Abstract
BACKGROUND In mastocytosis, the skin is almost invariably involved, and cutaneous symptoms deeply affect patients' quality of life. METHODS A retrospective observational analysis of patients affected by cutaneous mastocytosis (CM) and indolent systemic mastocytosis (ISM) treated with phototherapy/photochemotherapy (PUVA or NB-UVB) has been conducted. For each patient, total numbers of PUVA or NB-UVB exposures, the cumulative UV dose (J/cm2 ), serum tryptase profile, and pruritus, before and after treatment, according to the visual analogue scale (VAS) were considered. Skin lesions of each patient were assessed, before and after treatment, according to a cutaneous scale score. RESULTS Twenty patients affected by CM and ISM were studied; in particular, 10 patients received NB-UVB therapy, and other 10 patients received PUVA. A statistically significant mean reduction of pruritus in both groups (P < 0.01) was observed. The number of treatments necessary to obtain symptom relief was significantly lower in the PUVA group, but the mean exposure dose was significantly higher, if compared to the NB-UVB group. Serum tryptase levels showed a downward trend. The cutaneous score improved in both groups. LIMITATIONS This study was a retrospective study with a small sample size and without a control group. CONCLUSION This work provides evidence that both NB-UVB and PUVA represent a safe and useful second-line therapy of the cutaneous symptoms in mastocytosis.
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Affiliation(s)
- Valeria Brazzelli
- Institute of Dermatology, Department of Clinical-Surgical, Diagnostic and Pediatric Science, IRCCS Foundation Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Sara Grassi
- Institute of Dermatology, Department of Clinical-Surgical, Diagnostic and Pediatric Science, IRCCS Foundation Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Serena Merante
- Department of Haematology, IRCCS Foundation Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Vincenzo Grasso
- Institute of Dermatology, Department of Clinical-Surgical, Diagnostic and Pediatric Science, IRCCS Foundation Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Rachele Ciccocioppo
- First Department of Internal Medicine, IRCCS Foundation Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Grazia Bossi
- Department of Pediatrics, IRCCS Foundation Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Giovanni Borroni
- Institute of Dermatology, Department of Clinical-Surgical, Diagnostic and Pediatric Science, IRCCS Foundation Policlinico San Matteo, University of Pavia, Pavia, Italy
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Potential role of reduced environmental UV exposure as a driver of the current epidemic of atopic dermatitis. J Allergy Clin Immunol 2015; 136:1163-9. [DOI: 10.1016/j.jaci.2015.06.042] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 06/04/2015] [Accepted: 06/12/2015] [Indexed: 11/23/2022]
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Engebretsen K, Johansen J, Kezic S, Linneberg A, Thyssen J. The effect of environmental humidity and temperature on skin barrier function and dermatitis. J Eur Acad Dermatol Venereol 2015; 30:223-49. [DOI: 10.1111/jdv.13301] [Citation(s) in RCA: 151] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2015] [Accepted: 06/01/2015] [Indexed: 01/06/2023]
Affiliation(s)
- K.A. Engebretsen
- National Allergy Research Centre; Department of Dermato-Allergology; Gentofte University Hospital; University of Copenhagen; Hellerup Denmark
| | - J.D. Johansen
- National Allergy Research Centre; Department of Dermato-Allergology; Gentofte University Hospital; University of Copenhagen; Hellerup Denmark
| | - S. Kezic
- Coronel Institute of Occupational Health; Academic Medical Centre; 1105 AZ Amsterdam The Netherlands
| | - A. Linneberg
- Research Centre for Prevention and Health; Glostrup The Capital Region of Denmark Copenhagen Denmark
- Department of Clinical Experimental Research; Glostrup University Hospital; Glostrup Denmark
- Department of Clinical Medicine; Faculty of Health and Medical Sciences; University of Copenhagen; Copenhagen Denmark
| | - J.P. Thyssen
- National Allergy Research Centre; Department of Dermato-Allergology; Gentofte University Hospital; University of Copenhagen; Hellerup Denmark
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22
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Subramani PA, Hameed B, Michael RD. Effect of UV-B radiation on the antibody response of fish - implication on high altitude fish culture. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2014; 143:1-4. [PMID: 25579806 DOI: 10.1016/j.jphotobiol.2014.12.021] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/21/2014] [Revised: 12/19/2014] [Accepted: 12/22/2014] [Indexed: 10/24/2022]
Abstract
Literally, all living forms are either directly or indirectly dependent upon sun for energy. Radiation from sun is differentiated into several components of a spectrum based on the wavelength. Ultraviolet (UV) radiation may be one of the infamous radiations emitted by the sun. Ozone depletion is another critical factor by which UV induced ill-effects are intensified. Though there are numerous studies on effects of UV radiation on terrestrial organisms, its effect on freshwater and aquaculture ecosystems has been largely neglected. Here, we report that enhanced UV irradiation may suppress the primary and secondary antibody responses to a soluble protein antigen in fish. Fishes exposed for longer periods (80min) were particularly very sensitive to infection, as shown by our sensitivity index.
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Affiliation(s)
| | - Byju Hameed
- No. 35, Rakatchi Garden, Ganapathy, Coimbatore 641006, India
| | - R Dinakaran Michael
- Centre for Fish Immunology, School of Life Sciences, Vels University, Pallavaram, Chennai 600117, India.
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da Silva EZM, Jamur MC, Oliver C. Mast cell function: a new vision of an old cell. J Histochem Cytochem 2014; 62:698-738. [PMID: 25062998 PMCID: PMC4230976 DOI: 10.1369/0022155414545334] [Citation(s) in RCA: 421] [Impact Index Per Article: 38.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2014] [Accepted: 07/07/2014] [Indexed: 02/06/2023] Open
Abstract
Since first described by Paul Ehrlich in 1878, mast cells have been mostly viewed as effectors of allergy. It has been only in the past two decades that mast cells have gained recognition for their involvement in other physiological and pathological processes. Mast cells have a widespread distribution and are found predominantly at the interface between the host and the external environment. Mast cell maturation, phenotype and function are a direct consequence of the local microenvironment and have a marked influence on their ability to specifically recognize and respond to various stimuli through the release of an array of biologically active mediators. These features enable mast cells to act as both first responders in harmful situations as well as to respond to changes in their environment by communicating with a variety of other cells implicated in physiological and immunological responses. Therefore, the critical role of mast cells in both innate and adaptive immunity, including immune tolerance, has gained increased prominence. Conversely, mast cell dysfunction has pointed to these cells as the main offenders in several chronic allergic/inflammatory disorders, cancer and autoimmune diseases. This review summarizes the current knowledge of mast cell function in both normal and pathological conditions with regards to their regulation, phenotype and role.
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Affiliation(s)
- Elaine Zayas Marcelino da Silva
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil (EZMDS, MCJ, CO)
| | - Maria Célia Jamur
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil (EZMDS, MCJ, CO)
| | - Constance Oliver
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil (EZMDS, MCJ, CO)
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24
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Salgado CM, Silver RB, Bauer BS, Basu D, Schmitt L, Khakoo Y, Reyes-Múgica M. Skin of patients with large/giant congenital melanocytic nevi shows increased mast cells. Pediatr Dev Pathol 2014; 17:198-203. [PMID: 24679055 DOI: 10.2350/14-02-1444-oa.1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Nevocytes (NC) and mastocytes (MC) have different progenitors but share stem cell factor as regulator/activator of NC and for differentiation/proliferation of MC. Both cell types express stem cell factor receptor CD117. We hypothesize that large/giant congenital melanocytic nevi (L/GCMN) may associate with MC hyperplasia. Forty-nine L/GCMN were examined, 12 samples from uninvolved skin of L/GCMN patients and 6 control skin samples studied with Giemsa and immunohistochemistry for CD117 and MC-tryptase. Picrosirius red (PR) was used to assess fibrosis. Digital images were used to count MC/mm(2) using ImageJ software. Western blot (WB) for MC-tryptase in 12 GCMN and 12 non-nevus samples was performed. Analysis of variance (Tukey) and Pearson statistical tests were applied. Increased MCs were observed in nevus tissue (75.1 ± 35.3 MCs/mm(2)) and in uninvolved skin (53.74 ± 27.7 MC/ mm(2)). P = 0.109 from patients with L/GCMN, compared with controls from individuals without L/GCMN (28.74 ± 8.4 MC/mm(2)); P = 0.001 supported by results of WB analysis for tryptase. A positive trend toward correlation of MC numbers with fibrosis, assessed by PR staining fell short of statistical significance (r = 0.245; P = 0.086); no difference in fibrosis was found between nevus and non-nevus skin from patients with L/GCMN (P = 0.136). We found a higher density of MC, both in normal-appearing skin and nevus areas of L/GCMN patients, compared with control skin samples from individuals without nevi. Given the abnormal wound healing and allergic reactions described in L/GCMN patients, these findings suggest a potential role for MC in the biology of L/GCMN, making them a potential target for therapeutic intervention.
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Affiliation(s)
- Cláudia M Salgado
- 1 Department of Pathology, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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25
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Khafagy NH, Salem SAM, Ghaly EG. Comparative study of systemic psoralen and ultraviolet A and narrowband ultraviolet B in treatment of chronic urticaria. PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE 2013; 29:12-7. [PMID: 23281692 DOI: 10.1111/phpp.12008] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Accepted: 09/12/2012] [Indexed: 11/30/2022]
Abstract
BACKGROUND Previous success rates of psoralen and ultraviolet A (PUVA) and narrowband UVB (NB-UVB) in the treatment of chronic urticaria are reported in few studies with no previous reports on the comparable efficacy of both modalities in the disease. AIM We aimed to compare the efficacy of PUVA versus NB-UVB in the treatment of chronic urticaria. METHODS Twenty-four patients with chronic urticaria were included and divided into two groups: 12 patients subjected to PUVA and 12 subjected to NB-UVB. They were compared according to the urticaria Total Severity Score (TSS) before and after treatment, cumulative dose, and side effects. RESULTS There was a statistically significant decrease in urticaria TSS in both the NB-UVB- and PUVA-treated groups after than before treatment (P < 0.05), with no significant difference between both groups regarding the percentage of improved patients and the mean decrease of urticaria TSS (P > 0.05). Gastrointestinal upset was reported at a significantly higher percentage in the PUVA-treated group than in the NB-UVB-treated group. CONCLUSION Both NB-UVB and PUVA show comparable efficacy in the treatment of chronic urticaria with minimal reversible side effects.
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Affiliation(s)
- Naziha Hafez Khafagy
- Department of Dermatology and Venereology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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26
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Saeed AK, Salmo N. Epidermal growth factor receptor expression in mice skin upon ultraviolet B exposure - Seborrheic Keratosis as a coincidental and unique finding. Adv Biomed Res 2012; 1:59. [PMID: 23326790 PMCID: PMC3544126 DOI: 10.4103/2277-9175.100178] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2012] [Accepted: 05/08/2012] [Indexed: 12/03/2022] Open
Abstract
Background: Ultraviolet B (UVB) is the most damaging component of sunlight. It rapidly activates the epidermal growth factor receptor (EGFR) and generates reactive oxygen species (ROS) in excessive quantities that quickly overwhelm tissue antioxidants. Setting and Design: To demonstrate the effects of UVB radiation on EGFR expression in mice skin and to evaluate the role of antioxidants in the exposed group. Materials and Methods: After obtaining the approval of the ethical committee, forty mice from BALB/c strain were used in this experiment and were allocated into 3 groups; 10 (control group); 15 (exposure group); and 15 (exposed and treated with antioxidants). Antioxidants were administered through subcutaneous injection. Skin biopsies from all groups were stained with EGFR antibodies. Total antioxidant status (TAS) was evaluated in all groups. Statistical Analysis: The data obtained were analyzed using ANOVA, Duncan's test, and Pearson's Correlation. Results: The highest EGFR expression in exposure group was of score 3+ (53%). The highest EGFR expression in treatment group was score 0 (40%). Apoptotic bodies and dermal mast cells increased in exposure group while decreased in treatment group. The mean values for TAS were measured for each group; control group = 1.2 mmol/l; exposure group = 0.87 mmol/l; treatment group =1.3 mmol/l. Conclusions: UVB led to Seborrheic Keratosis (SK) in mice through enhancement of EGFR expression. Antioxidants effectively reduced UVB-induced SK, reduced epidermal changes, apoptotic bodies, and decreased dermal mast cells. TAS measurement declined in exposure group, while it was within normal range in most treated cases.
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Affiliation(s)
- Azad K Saeed
- Department of Pathology, College of Veterinary Medicine, Sulaimani University/Kurdistan, Iraq
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27
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Cozzi SJ, Ogbourne SM, James C, Rebel HG, de Gruijl FR, Ferguson B, Gardner J, Lee TT, Larcher T, Suhrbier A. Ingenol Mebutate Field-Directed Treatment of UVB-Damaged Skin Reduces Lesion Formation and Removes Mutant p53 Patches. J Invest Dermatol 2012; 132:1263-71. [DOI: 10.1038/jid.2011.418] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Sarchio SNE, Kok LF, O'Sullivan C, Halliday GM, Byrne SN. Dermal mast cells affect the development of sunlight-induced skin tumours. Exp Dermatol 2012; 21:241-8. [PMID: 22276860 DOI: 10.1111/j.1600-0625.2012.01438.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Ultraviolet (UV) radiation contained in sunlight is considered a major risk in the induction of skin cancer. While mast cells are best known for their role in allergic responses, they have also been shown to play a crucial role in suppressing the anti-tumour immune response following UV exposure. Evidence is now emerging that UV may also trigger mast cell release of cutaneous tissue remodelling and pro-angiogenic factors. In this review, we will focus on the cellular and molecular mechanisms by which UV recruits and then activates mast cells to initiate and promote skin cancer development.
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Affiliation(s)
- Seri N E Sarchio
- Discipline of Infectious Diseases and Immunology, Sydney Medical School, University of Sydney, Sydney, NSW, Australia
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29
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Artuc M, Guhl S, Babina M, Unger T, Steckelings UM, Zuberbier T. Mast cell-derived TNF-α and histamine modify IL-6 and IL-8 expression and release from cutaneous tumor cells. Exp Dermatol 2011; 20:1020-2. [PMID: 21995333 DOI: 10.1111/j.1600-0625.2011.01377.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
The coincidence of skin tumors and elevated mast cell (MC) numbers has been known for many years. However, it has remained controversial whether, in this context, MCs promote or inhibit tumor growth. Addressing this problem, different melanoma and squamous cell carcinoma cell lines were co-cultivated with primary, dermal MC for 24 h and gene or protein expression of cytokines tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8) estimated. Co-culture with MCs led to an increase in IL-8 gene expression and IL-8 protein release from melanoma cells and IL-6 and IL-8 gene expression and protein release from squamous cell carcinoma cells, respectively. Moreover induction of IL-6 and IL-8 was primarily regulated by MC-derived TNF-α. Our data suggest an interplay between MCs and tumor cells, which results in altered cytokine release and may, thus, have an impact on tumor growth, invasion and neovascularisation.
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Abstract
Mast cells (MCs) were first described by Paul Ehrlich 1 in his doctoral thesis. MCs have long been implicated in the pathogenesis of allergic reactions and certain protective responses to parasites. As most tumors contain inflammatory cell infiltrates, which often include plentiful MCs, the question as to the possible contribution of MCs to tumor development has progressively been emerging. In this chapter, the specific involvement of MCs in tumor biology and tumor fate will be considered, with particular emphasis on the capacity of these cells to stimulate tumor growth by promoting angiogenesis and lymphangiogenesis. Data from experimental carcinogenesis and from different tumor settings in human pathology will be summarized. Information to be presented will suggest that MCs may serve as a novel therapeutic target for cancer treatment.
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31
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Accumulation of CD1a-positive Langerhans cells and mast cells in actinic cheilitis. J Mol Histol 2010; 41:357-65. [DOI: 10.1007/s10735-010-9297-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2010] [Accepted: 09/07/2010] [Indexed: 12/24/2022]
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Frossi B, Gri G, Tripodo C, Pucillo C. Exploring a regulatory role for mast cells: 'MCregs'? Trends Immunol 2010; 31:97-102. [PMID: 20149743 DOI: 10.1016/j.it.2009.12.007] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2009] [Revised: 12/22/2009] [Accepted: 12/23/2009] [Indexed: 11/28/2022]
Abstract
Regulatory cells can mould the fate of the immune response by direct suppression of specific subsets of effector cells, or by redirecting effectors against invading pathogens and infected or neoplastic cells. These functions have been classically, although not exclusively, ascribed to different subsets of T cells. Recently, mast cells have been shown to regulate physiological and pathological immune responses, and thus to act at the interface between innate and adaptive immunity assuming different functions and behaviors at discrete stages of the immune response. Here, we focus on these poorly defined, and sometimes apparently conflicting, functions of mast cells.
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Affiliation(s)
- Barbara Frossi
- Department of Biomedical Science and Technology, University of Udine, P. le M. Kolbe 4, 33100 Udine, Italy
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Ju MJ, Qiu SJ, Gao Q, Fan J, Cai MY, Li YW, Tang ZY. Combination of peritumoral mast cells and T-regulatory cells predicts prognosis of hepatocellular carcinoma. Cancer Sci 2009; 100:1267-74. [PMID: 19432885 PMCID: PMC11159676 DOI: 10.1111/j.1349-7006.2009.01182.x] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2009] [Revised: 03/28/2009] [Accepted: 03/29/2009] [Indexed: 12/12/2022] Open
Abstract
The peritumoral inflammatory environment is critical for the progression of intrahepatic recurrence of hepatocellular carcinoma (HCC) after curative resections. Here, we investigated the relevance of peritumoral mast cells (MCs) to HCC outcomes. Peritumoral tryptase(+) MCs in addition to Foxp3(+) T-regulatory cells (Tregs) were evaluated using immunohistochemistry enumeration in tissue microarrays containing 207 randomly selected HCC patients. Clinicopathological factors and postoperative outcomes were compared between high and low subgroups of MCs or Tregs. Compared to low denstiy, higher peritumoral MCs were associated with poorer clinical outcomes, and independently related to elevated 5-year recurrence incidence (54.1%vs 39.2%, P = 0.026). High-dense MCs were especially related to increased probability of early recurrence (within 2 years) (P = 0.004). We also found that peritumoral Tregs were positively correlated with MCs in density (r = 0.353, P < 0.001) and reversely related to HCC outcomes. Notably, MCs in combination with Tregs displayed better prognostic performances than MCs alone (area under curve [AUC](survival) = 0.629 vs 0.589, AUC(recurrence) = 0.632 vs 0.591). Moreover, MCs were positively correlated to alanine aminotransferase, a serum inflammatory marker (P = 0.014). Therefore, peritumoral MCs are promising prognostic parameters for HCC mainly through inflammation response-related mechanisms, and we propose that MCs and Tregs may cooperate with each other and result in poorer prognosis.
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Affiliation(s)
- Min-Jie Ju
- Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School of Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Shanghai, China
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The controversial role of mast cells in tumor growth. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2009; 275:89-131. [PMID: 19491054 DOI: 10.1016/s1937-6448(09)75004-x] [Citation(s) in RCA: 82] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Mast cells (MCs) were first described by Paul Ehrlich (Beiträge zur Theorie und Praxis der Histologischen Färbung, Thesis, Leipzig University, 1878). They have long been implicated in the pathogenesis of allergic reactions and protective responses to parasites. However, their functional role has been found to be complex and multifarious. MCs are also involved in various cell-mediated immune reactions and found in tissues from multiple disease sites, and as a component of the host reaction to bacteria, parasite, and even virus infections. They also participate in angiogenic and tissue repair processes after injury. The importance of a possible functional link between chronic inflammation and cancer has long been recognized. As most tumors contain inflammatory cell infiltrates, which often include plentiful MCs, a possible contribution of these cells to tumor development has emerged. In this review, general biology of mast cells, their development, anatomical distribution, and phenotype as well as their secretory products will first be discussed. The specific involvement of MCs in tumor biology and tumor fate will then be considered, with particular emphasis on their capacity to stimulate tumor growth by promoting angiogenesis and lymphangiogenesis. Finally, it is suggested that mast cells may serve as a novel therapeutic target for cancer treatment.
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35
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Wasiuk A, de Vries VC, Hartmann K, Roers A, Noelle RJ. Mast cells as regulators of adaptive immunity to tumours. Clin Exp Immunol 2008; 155:140-6. [PMID: 19077084 DOI: 10.1111/j.1365-2249.2008.03840.x] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
The observation that mast cells accumulate at the periphery of growing tumours is now well documented, and the loss of mast cells correlates with reduced tumour growth. The role of mast cells as innate regulators of both inflammatory and immunosuppressive responses slowly becomes clear as novel tools become available. This review will address the role of mast cells in tumours and how they can interact with the local immune environment to mediate immune suppression contributing to tumour escape.
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Affiliation(s)
- A Wasiuk
- Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756, USA
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36
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Callaghan TM, Wilhelm KP. A review of ageing and an examination of clinical methods in the assessment of ageing skin. Part I: Cellular and molecular perspectives of skin ageing. Int J Cosmet Sci 2008; 30:313-22. [DOI: 10.1111/j.1468-2494.2008.00454.x] [Citation(s) in RCA: 88] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Pos Z, Wiener Z, Pocza P, Racz M, Toth S, Darvas Z, Molnar V, Hegyesi H, Falus A. Histamine suppresses fibulin-5 and insulin-like growth factor-II receptor expression in melanoma. Cancer Res 2008; 68:1997-2005. [PMID: 18339882 DOI: 10.1158/0008-5472.can-07-2816] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
We previously showed that transgenic enhancement of histamine production in B16-F10 melanomas strongly supports tumor growth in C57BL/6 mice. In the present study, gene expression profiles of transgenic mouse melanomas, secreting different amounts of histamine, were compared by whole genome microarrays. Array results were validated by real-time PCR, and genes showing histamine-affected behavior were further analyzed by immunohistochemistry. Regulation of histamine-coupled genes was investigated by checking the presence and functional integrity of all four known histamine receptors in experimental melanomas and by administering histamine H1 receptor (H1R) and H2 receptor (H2R) antagonists to tumor-bearing mice. Finally, an attempt was made to integrate histamine-affected genes in known gene regulatory circuits by in silico pathway analysis. Our results show that histamine enhances melanoma growth via H1R rather than through H2R. We show that H1R activation suppresses RNA-level expression of the tumor suppressor insulin-like growth factor II receptor (IGF-IIR) and the antiangiogenic matrix protein fibulin-5 (FBLN5), decreases their intracellular protein levels, and also reduces their availability in the plasma membrane and extracellular matrix, respectively. Pathway analysis suggests that because plasma membrane-bound IGF-IIR is required to activate matrix-bound, latent transforming growth factor-beta1, a factor suggested to sustain FBLN5 expression, the data can be integrated in a known antineoplastic regulatory pathway that is suppressed by H1R. On the other hand, we show that engagement of H2R also reduces intracellular protein pools of IGF-IIR and FBLN5, but being a downstream acting posttranslational effect with minimal consequences on exported IGF-IIR and FBLN5 protein levels, H2R is rather irrelevant compared with H1R in melanoma.
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Affiliation(s)
- Zoltan Pos
- Department of Genetics, Cell, and Immunobiology, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary
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Byrne SN, Limón-Flores AY, Ullrich SE. Mast cell migration from the skin to the draining lymph nodes upon ultraviolet irradiation represents a key step in the induction of immune suppression. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2008; 180:4648-55. [PMID: 18354188 PMCID: PMC2391302 DOI: 10.4049/jimmunol.180.7.4648] [Citation(s) in RCA: 117] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The UV radiation in sunlight is the primary cause of skin cancer. UV is also immunosuppressive and numerous studies have shown that UV-induced immune suppression is a major risk factor for skin cancer induction. Previous studies demonstrated that dermal mast cells play a critical role in the induction of immune suppression. Mast cell-deficient mice are resistant to the immunosuppressive effects of UV radiation, and UV-induced immune suppression can be restored by injecting bone marrow-derived mast cells into the skin of mast cell- deficient mice. The exact process however, by which mast cells contribute to immune suppression, is not known. In this study, we show that one of the first steps in the induction of immune suppression is mast cell migration from the skin to the draining lymph nodes. UV exposure, in a dose-dependent manner, causes a significant increase in lymph node mast cell numbers. When GFP(+) skin was grafted onto mast cell-deficient mice, we found that GFP(+) mast cells preferentially migrated into the lymph nodes draining the skin. The mast cells migrated primarily to the B cell areas of the draining nodes. Mast cells express CXCR4(+) and UV exposure up-regulated the expression of its ligand CXCL12 by lymph node B cells. Treating UV-irradiated mice with a CXCR4 antagonist blocked mast cell migration and abrogated UV-induced immune suppression. Our findings indicate that UV-induced mast cell migration to draining lymph nodes, mediated by CXCR4 interacting with CXCL12, represents a key early step in UV-induced immune suppression.
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Affiliation(s)
- Scott N. Byrne
- Dermatology Research Unit, Melanoma and Skin Cancer Research Institute, Sydney Cancer Centre, Royal Prince Alfred Hospital at University of Sydney, Australia
| | - Alberto Y. Limón-Flores
- Department of Immunology and The Center for Cancer Immunology Research, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas, 77030, USA
| | - Stephen E. Ullrich
- Department of Immunology and The Center for Cancer Immunology Research, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas, 77030, USA
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Saadé NE, Farhat O, Rahal O, Safieh-Garabedian B, Le Bars D, Jabbur SJ. Ultra violet-induced localized inflammatory hyperalgesia in awake rats and the role of sensory and sympathetic innervation of the skin. Brain Behav Immun 2008; 22:245-56. [PMID: 17884331 DOI: 10.1016/j.bbi.2007.08.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2007] [Revised: 08/03/2007] [Accepted: 08/09/2007] [Indexed: 01/22/2023] Open
Abstract
Exposure to mid range ultrat violet radiations (UVBs) has been shown to produce systemic inflammation and hyperalgesia in mice [Saadé, N.E., Nasr, I.W., Massaad, C.A., Safieh-Garabedian, B., Jabbur, S.J., Kanaan, S.A., 2000. Modulation of ultraviolet-induced hyperalgesia and cytokine upregulation by interleukins 10 and 13. Br. J. Pharmacol. 131, 1317-1324]. Our aim was to characterize a new rat model of localized exposure to UVB and to determine the role of skin innervation in the observed hyperalgesia and cytokine upregulation. In several groups of rats one hindpaw was exposed to UVB (250-350 mJ/cm(2)) and this was followed by the application, to the plantar area of the paw, of either Von Frey hairs or a few acetone drops to measure tactile and cold allodynia, respectively. Thermal hyperalgesia was assessed by the paw withdrawal latency and duration. Cytokine levels were determined, by ELISA, in processed samples of skin tissue isolated from the exposed and non-exposed paws. UVB induced a biphasic thermal hyperalgesia and cold and tactile allodynia with an early phase that peaked at 3-6h and disappeared at 24h and a late phase with a peak at 48 h and recovery at 72-h post-exposure. Tumor necrosis factor, interleukins 1 beta, 6, 8, 10 and NGF levels were significantly increased following the same biphasic temporal pattern. Chemical ablation of capsaicin sensitive afferents and guanethidine injection produced significant alteration of the hyperalgesia and allodynia. The increase in cytokine levels by UVB was also altered by both treatments. The present study describes a new animal model for localized UVB-induced inflammatory hyperalgesia and provides evidence about the involvement of neurogenic mechanisms in the observed hyperalgesia and upregulation of proinflammatory mediators.
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Affiliation(s)
- Nayef E Saadé
- Department of Human Morphology, Faculty of Medicine, American University of Beirut, Riad E1 Solh Beirut, Beirut 1107-2020, Lebanon.
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Metz M, Grimbaldeston MA, Nakae S, Piliponsky AM, Tsai M, Galli SJ. Mast cells in the promotion and limitation of chronic inflammation. Immunol Rev 2007; 217:304-28. [PMID: 17498068 DOI: 10.1111/j.1600-065x.2007.00520.x] [Citation(s) in RCA: 226] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Observations of increased numbers of mast cells at sites of chronic inflammation have been reported for over a hundred years. Light and electron microscopic evidence of mast cell activation at such sites, taken together with the known functions of the diverse mediators, cytokines, and growth factors that can be secreted by appropriately activated mast cells, have suggested a wide range of possible functions for mast cells in promoting (or suppressing) many features of chronic inflammation. Similarly, these and other lines of evidence have implicated mast cells in a variety of adaptive or pathological responses that are associated with persistent inflammation at the affected sites. Definitively characterizing the importance of mast cells in chronic inflammation in humans is difficult. However, mice that genetically lack mast cells, especially those which can undergo engraftment with wildtype or genetically altered mast cells, provide a means to investigate the importance of mast cells and specific mast cell functions or products in diverse models of chronic inflammation. Such work has confirmed that mast cells can significantly influence multiple features of chronic inflammatory responses, through diverse effects that can either promote or, perhaps more surprisingly, suppress aspects of these responses.
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Affiliation(s)
- Martin Metz
- Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5324, USA
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Sime S, Reeve VE. Protection from Inflammation, Immunosuppression and Carcinogenesis Induced by UV Radiation in Mice by Topical Pycnogenol®¶. Photochem Photobiol 2007. [DOI: 10.1111/j.1751-1097.2004.tb00009.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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42
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Aguiar ALM, Martins CJ, Meuser-Batista M, Carvalho VF, Barreto EO, E Silva PM, Corte-Real S, Baetas-Da-Cruz W. A case of keratoacanthoma centrifugum marginatum with a curious mast cell accumulation at tumour sites. J Eur Acad Dermatol Venereol 2007; 21:429-31. [PMID: 17309493 DOI: 10.1111/j.1468-3083.2006.01928.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Hwang H, Chen T, Nines RG, Shin HC, Stoner GD. Photochemoprevention of UVB-induced skin carcinogenesis in SKH-1 mice by brown algae polyphenols. Int J Cancer 2006; 119:2742-9. [PMID: 17019718 DOI: 10.1002/ijc.22147] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Chronic exposure of the skin to ultraviolet B (UVB) radiation induces oxidative stress, which plays a crucial role in the induction of skin cancer. In this study, the effect of dietary feeding and topical application of brown algae polyphenols on UVB radiation-induced skin carcinogenesis in SKH-1 mice was investigated. SKH-1 hairless mice were randomly divided into 9 groups, including control, UVB control and treatment groups. They were treated orally (0.1% and 0.5% with AIN-76 diet, w/w) and topically (3 and 6 mg/0.2 ml of vehicle) with brown algae polyphenols and irradiated with UVB for 26 weeks. Dietary feeding (0.1% and 0.5%) of brown algae polyphenols significantly reduced tumor multiplicity (45% and 56%) and tumor volume (54% and 65%), and topical administration (3 and 6 mg) significantly decreased tumor multiplicity (60% and 46%) and tumor volume (66% and 57%), respectively, per tumor-bearing mouse. Dietary feeding and topical administration of the polyphenols also inhibited tumor incidence by 6% and 21%, respectively, but the results were not significant. Dietary and topical administration of the polyphenols markedly inhibited cyclooxygenase-2 activity and cell proliferation. These observations show that brown algae polyphenols have an antiphotocarcinogenic effect which may be associated with the prevention of UVB-induced oxidative stress, inflammation, and cell proliferation in the skin.
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Affiliation(s)
- Hyejeong Hwang
- Chemoprevention and Support Program, Division of Hematology and Oncology, Department of Internal Medicine, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210, USA
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Depinay N, Hacini F, Beghdadi W, Peronet R, Mécheri S. Mast Cell-Dependent Down-Regulation of Antigen-Specific Immune Responses by Mosquito Bites. THE JOURNAL OF IMMUNOLOGY 2006; 176:4141-6. [PMID: 16547250 DOI: 10.4049/jimmunol.176.7.4141] [Citation(s) in RCA: 108] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
While probing host skin to search for blood vessels, the female Anopheles mosquito delivers Plasmodium parasites in the presence of saliva. Saliva from various blood-feeding vectors which contains several pharmacologically active components is believed to facilitate blood feeding as well as parasite transmission to the host. Recently, we found that mosquito saliva has the capacity to activate dermal mast cells and to induce local inflammatory cell influx. Our main objective in the present work is to investigate whether saliva, through mosquito bites, controls the magnitude of Ag-specific immune responses and whether this control is dependent on the mast cell-mediated inflammatory response. Using a mast cell knockin mouse model, we found that mosquito bites consistently induced MIP-2 in the skin and IL-10 in draining lymph nodes, and down-regulate Ag-specific T cell responses by a mechanism dependent on mast cells and mediated by IL-10. Our results provide evidence for new mechanisms which may operate during Plasmodium parasite transmission by mosquito bites.
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Affiliation(s)
- Nadya Depinay
- Unité des Réponses Précoces aux Parasites et Immunopathologie, Institut Pasteur, Paris, France
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Hernandez-Pigeon H, Jean C, Charruyer A, Haure MJ, Titeux M, Tonasso L, Quillet-Mary A, Baudouin C, Charveron M, Laurent G. Human keratinocytes acquire cellular cytotoxicity under UV-B irradiation. Implication of granzyme B and perforin. J Biol Chem 2006; 281:13525-13532. [PMID: 16524880 DOI: 10.1074/jbc.m512694200] [Citation(s) in RCA: 73] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Ultraviolet (UV) radiation from the sun is widely considered as a major cause of human skin photoaging and skin cancer. Granzyme B (GrB) and perforin (PFN) are two proteins contained in granules and implicated in one of the mechanisms by which cytotoxic lymphocytes and natural killer cells exert their cytotoxicity against virus-infected, alloreactive, or transformed cells. The distribution of GrB and PFN in the skin has received little attention. However, Berthou and co-workers (Berthou, C., Michel, L., Soulie, A., Jean-Louis, F., Flageul, B., Dubertret, L., Sigaux, F., Zhang, Y., and Sasportes, M. (1997) J. Immunol. 159, 5293-5300) described that, whereas freshly isolated epidermal cells did not express GrB or PFN, keratinocyte growth to confluence was associated with GrB and PFN mRNA and protein synthesis. In this work, we have investigated the possible role of UV-B on GrB and PFN expression in keratinocytes. We found that UV-B induces GrB and PFN expression in these cells through redox-, epidermal growth factor receptor-, and mitogen-activated protein kinase-dependent signaling. Furthermore, under UV irradiation, keratinocytes acquire a significant cytotoxicity, which is GrB and PFN dependent, toward a variety of cellular targets including transformed T-lymphocytes, melanocytes, and keratinocytes. This phenomenon may have important functional consequences in the regulation of skin inflammatory response and in the emergence of cancer skin.
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Affiliation(s)
- Hélène Hernandez-Pigeon
- INSERM U563, CPTP, Bat B, Pavillon Lefebvre, Place du Dr. Baylac, Centre Hospitalier Universitaire Purpan, BP 3028, 31024 Toulouse cedex 3, France.
| | - Christine Jean
- INSERM U563, CPTP, Bat B, Pavillon Lefebvre, Place du Dr. Baylac, Centre Hospitalier Universitaire Purpan, BP 3028, 31024 Toulouse cedex 3, France
| | - Alexandra Charruyer
- INSERM U563, CPTP, Bat B, Pavillon Lefebvre, Place du Dr. Baylac, Centre Hospitalier Universitaire Purpan, BP 3028, 31024 Toulouse cedex 3, France
| | - Marie-José Haure
- CERPER, Institut de Recherche Pierre Fabre, Laboratoire de Biologie Cellulaire Cutanée, Toulouse, France
| | - Matthias Titeux
- INSERM U563, CPTP, Bat B, Pavillon Lefebvre, Place du Dr. Baylac, Centre Hospitalier Universitaire Purpan, BP 3028, 31024 Toulouse cedex 3, France
| | - Laure Tonasso
- INSERM U563, CPTP, Bat B, Pavillon Lefebvre, Place du Dr. Baylac, Centre Hospitalier Universitaire Purpan, BP 3028, 31024 Toulouse cedex 3, France
| | - Anne Quillet-Mary
- INSERM U563, CPTP, Bat B, Pavillon Lefebvre, Place du Dr. Baylac, Centre Hospitalier Universitaire Purpan, BP 3028, 31024 Toulouse cedex 3, France
| | - Caroline Baudouin
- CERPER, Institut de Recherche Pierre Fabre, Laboratoire de Biologie Cellulaire Cutanée, Toulouse, France
| | - Marie Charveron
- CERPER, Institut de Recherche Pierre Fabre, Laboratoire de Biologie Cellulaire Cutanée, Toulouse, France
| | - Guy Laurent
- INSERM U563, CPTP, Bat B, Pavillon Lefebvre, Place du Dr. Baylac, Centre Hospitalier Universitaire Purpan, BP 3028, 31024 Toulouse cedex 3, France; Service d'Hématologie, Centre Hospitalier Universitaire Purpan, 31059 Toulouse, France
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Abstract
This paper reviews the role of mast cells in the development and progression of basal cell carcinoma, squamous cell carcinoma and malignant melanoma. Mast cells accumulate around cutaneous malignancies. Current evidence suggests that mast cells contribute to the tumorigenesis of cutaneous malignancies through four mechanisms. (1) Immunosuppression: Ultraviolet-B radiation, the most important initiator of cutaneous malignancies, activates mast cells. Upon irradiation of the skin, trans-urocanic acid in the epidermis isomerizes to cis-urocanic acid, which stimulates neuropeptide release from neural c-fibers. These neuropeptides in turn trigger histamine secretion from mast cells, leading to suppression of the cellular immune system. (2) Angiogenesis: Mast cells are the major source of vascular endothelial growth factor in basal cell carcinoma and malignant melanoma. Vascular endothelial growth factor is one of the most potent angiogenic factors, which also induces leakage of other angiogenic factors across the endothelial cell wall into the matrix. Mast cell proteases reorganize the stroma to facilitate endothelial cell migration. As well, heparin, the dominant mast cell proteoglycan, assists in blood-borne metastasis. (3) Degradation of extracellular matrix: Through its own proteases, and indirectly via interaction with other cells, mast cells participate in degradation of the matrix, which is required for tumor spread. (4) Mitogenesis: Mast cell mediators including fibroblast growth factor-2 and interleukin-8 are mitogenic to melanoma cells. Current evidence supports an accessory role for mast cells in the development and progression of cutaneous malignancies. Emerging data, however, also suggest that mast cells might, in fact, have opposing roles in tumor biology, and the microenvironment could polarize mast cells to possess either promoting or inhibitory effects on tumors.
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Affiliation(s)
- Sydney Ch'ng
- Wellington Regional Plastic, Maxillofacial and Burns Unit, Hutt Hospital, Wellington, New Zealand
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Legat FJ, Wolf P. Photodamage to the cutaneous sensory nerves: role in photoaging and carcinogenesis of the skin? Photochem Photobiol Sci 2006; 5:170-6. [PMID: 16465302 DOI: 10.1039/b508856a] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Chronic exposure to ultraviolet radiation (UVR) plays a significant role in aging and carcinogenesis of the skin. Sensory nerve fibers densely innervate all layers of the skin and get in close anatomical as well as functional contact with cellular components of the epidermis and dermis. In this review, we address the impact of acute and chronic UVR exposure on the cutaneous sensory nervous system and its mediators. We suggest that skin cell-derived nerve growth factor (NGF) and skin nerve-derived neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP) may play a central role in intrinsic aging as well as extrinsic (photo-) aging of the skin. In addition, we discuss the possible role of these mediators in photocarcinogenesis.
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Affiliation(s)
- Franz J Legat
- Research Unit for Photodermatology, Department of Dermatology, Medical University of Graz, Auenbruggerplatz 8, A-8036, Graz, Austria.
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Pós Z, Sáfrány G, Müller K, Tóth S, Falus A, Hegyesi H. Phenotypic profiling of engineered mouse melanomas with manipulated histamine production identifies histamine H2 receptor and rho-C as histamine-regulated melanoma progression markers. Cancer Res 2005; 65:4458-66. [PMID: 15899839 DOI: 10.1158/0008-5472.can-05-0011] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
In the present study, the impact of acquired neoplastic L-histidine decarboxylase (HDC) expression, and its direct consequence, the release of histamine in the tumor environment, was assessed on melanoma tumor progression. B16-F10 mouse melanoma cells were manipulated via stable transfection, and nine novel transgenic variants were generated in triplicates, constitutively expressing the full-length sense mouse HDC mRNA, a mock control, and an antisense HDC RNA segment, respectively. Establishing both primary skin tumors and lung metastases in C57BL/6 mice, the nine variants with different histamine-releasing capacities were subjected to a comprehensive comparative progression profiling in vivo. Our analyses showed trends of markedly accelerated tumor growth (P < 0.001), and moderately increased metastatic colony-forming potential (P = 0.010) along with rising levels of local histamine production. Using RNase protection assay for screening of the melanoma progression profile, and Western blotting for subsequent result validation, we looked for molecular progression markers affected by melanoma histamine secretion. Investigation of 21 functionally clustered markers associated with tumor proliferation, angiogenesis, invasivity, metastasis formation, local or systemic immunomodulation, and histamine signaling revealed positive correlations between histamine production, tumor histamine H2 receptor and rho-C expression (P < 0.001, P = 0.002, respectively). These observations confirm the involvement of histamine in the molecular machinery of melanoma progression.
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MESH Headings
- Animals
- Biomarkers, Tumor
- Cell Line, Tumor
- Disease Progression
- Female
- Gene Expression Profiling
- Gene Expression Regulation, Enzymologic
- Gene Expression Regulation, Neoplastic
- Histamine/biosynthesis
- Histamine Release/physiology
- Histidine Decarboxylase/biosynthesis
- Histidine Decarboxylase/genetics
- Histidine Decarboxylase/metabolism
- Lung Neoplasms/metabolism
- Lung Neoplasms/secondary
- Melanoma, Experimental/genetics
- Melanoma, Experimental/metabolism
- Melanoma, Experimental/pathology
- Mice
- Mice, Inbred C57BL
- RNA, Messenger/genetics
- Receptors, Histamine H2/metabolism
- Transfection
- ras Proteins
- rho GTP-Binding Proteins/metabolism
- rhoC GTP-Binding Protein
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Affiliation(s)
- Zoltán Pós
- Hungarian Academy of Sciences, Semmelweis University Molecular Immunology Research Group, National Research Institute for Radiobiology and Radiohygiene, Department of Genetics, Cell, and Immunobiology, Semmelweis University, Budapest, Hungary
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49
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Guhl S, Stefaniak R, Strathmann M, Babina M, Piazena H, Henz BM, Zuberbier T. Bivalent effect of UV light on human skin mast cells-low-level mediator release at baseline but potent suppression upon mast cell triggering. J Invest Dermatol 2005; 124:453-6. [PMID: 15675967 DOI: 10.1111/j.0022-202x.2004.23523.x] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Ultraviolet (UV) irradiation is an established treatment for inflammatory skin diseases, although the precise mode of action is still unclear. Activating and suppressive effects on mast cell (MC) mediator release have been described. The aim of this study was to investigate systematically the effects of UVB, UVA-1, and psoralen plus UVA-1 at therapeutic doses on skin-derived human MC. Baseline and stimulated release of histamine, tryptase, and of interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) were examined. In resting MC, UV light induced a slight, yet significant histamine release corresponding to enhanced surface levels of lysosome-associated membrane proteins (LAMP). In contrast, UV pre-treatment caused a marked suppression of the anti-IgE-induced histamine release, accompanied by a diminished, anti-IgE-mediated increase in LAMP expression. The secretion of IL-6, IL-8, and TNF-alpha was inhibited in resting and activated MC, suggesting a different mode of action. Regarding the importance of MC in a variety of allergic and inflammatory processes, our data show a high susceptibility of this cell type towards UV light, which seems to partially depend on the state of cellular activation. Immunosuppressive effects predominate in activated MC, thus corresponding with the beneficial effects in inflammatory diseases, whereas in resting MC, both stimulatory and inhibitory effects are observed.
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Affiliation(s)
- Sven Guhl
- Department of Dermatology and Allergy, Charité Campus Mitte, Schumannstr. 20/21, D-10117 Berlin, Germany
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Sime S, Reeve VE. Protection from inflammation, immunosuppression and carcinogenesis induced by UV radiation in mice by topical Pycnogenol. Photochem Photobiol 2004; 79:193-8. [PMID: 15068032 DOI: 10.1562/0031-8655(2004)079<0193:pfiiac>2.0.co;2] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Pycnogenol is a standardized extract of the bark of the French maritime pine, Pinus pinaster Ait., that has multiple biological effects, including antioxidant, anti-inflammatory and anticarcinogenic properties. This study describes the effect of topical application of lotions containing Pycnogenol to Skh:hr hairless mice undergoing minimally inflammatory daily exposures to solar-simulated UV radiation (SSUV). We report that concentrations of Pycnogenol of 0.05-0.2% applied to the irradiated dorsal skin immediately after exposure resulted in dose-dependent reduction of the inflammatory sunburn reaction, measured as its edema component. When mice received three consecutive daily exposures of minimally edematous SSUV, their ability to raise a contact hypersensitivity (CHS) reaction was suppressed by 54%. Pycnogenol lotions applied postirradiation reduced this immunosuppression to 22% (0.05% Pycnogenol) and 13% (0.1% Pycnogenol). Furthermore, when CHS was suppressed by 71% with exogenous treatment with cis-urocanic acid, the putative epidermal mediator of photoimmunosuppression, 0.2% Pycnogenol lotion reduced the immunosuppression to 18%. Chronic exposure to SSUV on 5 days/week for 10 weeks induced skin tumors from 11 weeks in both control mice and in mice receiving daily applications of 0.05% Pycnogenol, but tumor appearance was significantly delayed until 20 weeks in mice receiving 0.2% Pycnogenol. Furthermore, whereas 100% of control mice had at least one tumor by 30 weeks, and mice treated with 0.05% Pycnogenol by 33 weeks, the maximum tumor prevalence in mice treated with 0.2% Pycnogenol was significantly reduced to 85%, with some mice remaining tumor free. Average tumor multiplicity was also significantly reduced by 0.2% Pycnogenol, from 5.2 in control mice to 3.5 at 35 weeks. Thus, topical Pycnogenol offered significant and dose-dependent protection from SSUV-induced acute inflammation, immunosuppression and carcinogenesis, when applied to the skin after daily irradiation. Pycnogenol, therefore, in addition to its recognized health benefits in other organs, appears to have potential in providing photoprotection for humans in a complementary role with sunscreens, having demonstrable activity when applied to the skin after, rather than before, UV exposure.
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Affiliation(s)
- Suzann Sime
- Faculty of Veterinary Science, University of Sydney, Sydney, NSW, Australia
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