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1
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Harsini S, Rezaei N. Autoimmune diseases. Clin Immunol 2023. [DOI: 10.1016/b978-0-12-818006-8.00001-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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2
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Pascoal LB, Palma BB, Chaim FHM, de Castro MM, Damázio TA, Franceschini APMDF, Milanski M, Velloso LA, Leal RF. New translational and experimental insights into the role of pro-resolving lipid mediators in inflammatory bowel disease. World J Exp Med 2022; 12:1-15. [PMID: 35096550 PMCID: PMC8771592 DOI: 10.5493/wjem.v12.i1.1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Revised: 10/21/2021] [Accepted: 01/08/2022] [Indexed: 02/06/2023] Open
Abstract
The resolution of inflammation is an active process, guided by specialized pro-resolution lipid mediators (SPMs). These mediators originate from polyunsaturated fatty acids, such as omega-3. Sufficient evidence suggests that the beneficial effects attributed to omega-3 are, at least in part, the result of the immunomodulatory action of the SPMs, which act systemically by overcoming inflammation and repairing tissue damage, without suppressing the immune response. Recent studies suggest that an imbalance in the synthesis and/or activity of these compounds may be associated with the pathogenesis of several inflammatory conditions, such as inflammatory bowel disease (IBD). Thus, this review highlights the advances made in recent years with regard to the endo-genous synthesis and the biological role of lipoxins, resolvins, protectins, and maresins, as well as their precursors, in the regulation of inflammation; and provides an update on the participation of these mediators in the development and evolution of IBD and the therapeutic approaches that these immunomodulating substances are involved in this context.
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Affiliation(s)
- Lívia Bitencourt Pascoal
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas, Campinas 13083-878, São Paulo, Brazil
| | - Bruna Biazon Palma
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas, Campinas 13083-878, São Paulo, Brazil
| | - Fabio Henrique Mendonça Chaim
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas, Campinas 13083-878, São Paulo, Brazil
| | - Marina Moreira de Castro
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas, Campinas 13083-878, São Paulo, Brazil
- Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas, Campinas 13083-878, São Paulo, Brazil
| | - Tiago Andrade Damázio
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas, Campinas 13083-878, São Paulo, Brazil
| | - Ana Paula Menezes de Freitas Franceschini
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas, Campinas 13083-878, São Paulo, Brazil
| | - Marciane Milanski
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas, Campinas 13083-878, São Paulo, Brazil
- Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas, Campinas 13083-878, São Paulo, Brazil
| | - Lício Augusto Velloso
- Laboratory of Cell Signaling, School of Medical Sciences, University of Campinas, Campinas 13083-864, São Paulo, Brazil
| | - Raquel Franco Leal
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas, Campinas 13083-878, São Paulo, Brazil
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3
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Wu D, Ye X, Linhardt RJ, Liu X, Zhu K, Yu C, Ding T, Liu D, He Q, Chen S. Dietary pectic substances enhance gut health by its polycomponent: A review. Compr Rev Food Sci Food Saf 2021; 20:2015-2039. [PMID: 33594822 DOI: 10.1111/1541-4337.12723] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 01/17/2021] [Accepted: 01/19/2021] [Indexed: 12/15/2022]
Abstract
Pectic substances, one of the cell wall polysaccharides, exist widespread in vegetables and fruits. A surge of recent research has revealed that pectic substances can inhibit gut inflammation and relieve inflammatory bowel disease symptoms. However, physiological functions of pectins are strongly structure dependent. Pectic substances are essentially heteropolysaccharides composed of homogalacturonan and rhamnogalacturonan backbones substituted by various neutral sugar sidechains. Subtle changes in the architecture of pectic substances may remarkably influence the nutritional function of gut microbiota and the host homeostasis of immune system. In this context, developing a structure-function understanding of how pectic substances have an impact on an inflammatory bowel is of primary importance for diet therapy and new drugs. Therefore, the present review has summarized the polycomponent nature of pectic substances, the activities of different pectic polymers, the effects of molecular characteristics and the underlying mechanisms of pectic substances. The immunomodulated property of pectic substances depends on not only the chemical composition but also the physical structure characteristics, such as molecular weight (Mw ) and chain conformation. The potential mechanisms by which pectic substances exert their protective effects are mainly reversing the disordered gut microbiota, regulating immune cells, enhancing barrier function, and inhibiting pathogen adhesion. The manipulation of pectic substances on gut health is sophisticated, and the link between structural specificity of pectins and selective regulation needs further exploration.
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Affiliation(s)
- Dongmei Wu
- National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Integrated Research Base of Southern Fruit and Vegetable Preservation Technology, Zhejiang International Scientific and Technological Cooperation Base of Health Food Manufacturing and Quality Control, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China
| | - Xingqian Ye
- National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Integrated Research Base of Southern Fruit and Vegetable Preservation Technology, Zhejiang International Scientific and Technological Cooperation Base of Health Food Manufacturing and Quality Control, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China.,Fuli Institute of Food Science, Zhejiang University, Hangzhou, China.,Ningbo Research Institute, Zhejiang University, Hangzhou, China
| | - Robert J Linhardt
- Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, USA
| | - Xuwei Liu
- UMR408, Sécurité et Qualité des Produits d'Origine Végétale (SQPOV), INRAE, Avignon, France
| | - Kai Zhu
- National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Integrated Research Base of Southern Fruit and Vegetable Preservation Technology, Zhejiang International Scientific and Technological Cooperation Base of Health Food Manufacturing and Quality Control, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China
| | - Chengxiao Yu
- National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Integrated Research Base of Southern Fruit and Vegetable Preservation Technology, Zhejiang International Scientific and Technological Cooperation Base of Health Food Manufacturing and Quality Control, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China
| | - Tian Ding
- National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Integrated Research Base of Southern Fruit and Vegetable Preservation Technology, Zhejiang International Scientific and Technological Cooperation Base of Health Food Manufacturing and Quality Control, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China
| | - Donghong Liu
- National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Integrated Research Base of Southern Fruit and Vegetable Preservation Technology, Zhejiang International Scientific and Technological Cooperation Base of Health Food Manufacturing and Quality Control, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China
| | - Qiaojun He
- Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Shiguo Chen
- National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Integrated Research Base of Southern Fruit and Vegetable Preservation Technology, Zhejiang International Scientific and Technological Cooperation Base of Health Food Manufacturing and Quality Control, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China.,Fuli Institute of Food Science, Zhejiang University, Hangzhou, China.,Ningbo Research Institute, Zhejiang University, Hangzhou, China
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4
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Busch MA, Gröndahl B, Knoll RL, Pretsch L, Doganci A, Hoffmann I, Kullmer U, Bähner V, Zepp F, Meyer CU, Gehring S. Patterns of mucosal inflammation in pediatric inflammatory bowel disease: striking overexpression of IL-17A in children with ulcerative colitis. Pediatr Res 2020; 87:839-846. [PMID: 31261370 DOI: 10.1038/s41390-019-0486-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Revised: 06/13/2019] [Accepted: 06/18/2019] [Indexed: 12/19/2022]
Abstract
BACKGROUND Aberrant immune responses play a key role in the pathogenesis of inflammatory bowel disease (IBD). Most studies conducted to delineate the underlying molecular mechanisms focus on adults; an understanding of these mechanisms in children remains to be determined. Here, cytokines and transcription factors produced by immune cells within the intestinal mucosa of pediatric patients stricken with ulcerative colitis (UC) and Crohn's disease (CD) are characterized; potential diagnostic and therapeutic targets are identified. METHODS Fifty-two pediatric IBD and non-IBD patients were enrolled in the study. Specimens were taken during ileocolonoscopy. Expression of 16 genes that encode cytokines or transcription molecules was determined by quantitative polymerase chain reaction. Clinical data were collected via retrospective chart review. RESULTS Overexpression of interleukin-17A (IL-17A) was evident in children with UC compared to both non-IBD and CD patients. IL-22 was strongly increased in UC patients only. Typical proinflammatory and immunoregulatory cytokines were pronounced in IBD patients, although to a lower extent in the latter case. Clustered gene expression enabled differentiation between UC and non-IBD patients. CONCLUSION Our findings highlight the crucial involvement of IL-17A immunity in the early course of IBD, particularly UC, and the potential value of gene panels in diagnosing pediatric IBD.
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Affiliation(s)
- Meike A Busch
- Children's Hospital, University Medical Center, Johannes Gutenberg-University, Mainz, Germany
| | - Britta Gröndahl
- Children's Hospital, University Medical Center, Johannes Gutenberg-University, Mainz, Germany
| | - Rebecca L Knoll
- Children's Hospital, University Medical Center, Johannes Gutenberg-University, Mainz, Germany
| | - Leah Pretsch
- Children's Hospital, University Medical Center, Johannes Gutenberg-University, Mainz, Germany
| | - Aysefa Doganci
- Children's Hospital, University Medical Center, Johannes Gutenberg-University, Mainz, Germany
| | - Isabell Hoffmann
- Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center, Johannes Gutenberg-University, Mainz, Germany
| | - Ulrike Kullmer
- Children's Hospital, University Medical Center, Johannes Gutenberg-University, Mainz, Germany
| | - Viola Bähner
- Children's Hospital, University Medical Center, Johannes Gutenberg-University, Mainz, Germany
| | - Fred Zepp
- Children's Hospital, University Medical Center, Johannes Gutenberg-University, Mainz, Germany
| | - Claudius U Meyer
- Children's Hospital, University Medical Center, Johannes Gutenberg-University, Mainz, Germany
| | - Stephan Gehring
- Children's Hospital, University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
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Nie N, Bai C, Song S, Zhang Y, Wang B, Li Z. Bifidobacterium plays a protective role in TNF-α-induced inflammatory response in Caco-2 cell through NF-κB and p38MAPK pathways. Mol Cell Biochem 2020; 464:83-91. [PMID: 31741130 DOI: 10.1007/s11010-019-03651-3] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Accepted: 11/08/2019] [Indexed: 12/17/2022]
Abstract
Kawasaki disease is an immune-mediated acute, systemic vasculitis and is the leading cause of acquired heart disease in children in the developed world. Bifidobacterium (BIF) is one of the dominant bacteria in the intestines of humans and many mammals and is able to adjust the intestinal flora disorder. The Caco-2 cell monolayers were treated with tumor necrosis factor-α (TNF-α) at 10 ng/ml for 24 h to induce the destruction of intestinal mucosal barrier system. Cells viability was detected through Cell Counting Kit-8 assay. Cell apoptosis was measured by flow cytometry and the expression of apoptosis related proteins was also detected through Western blot. The level of pro-inflammatory cytokines interleukin-6 (IL-6) and IL-8 was detected through ELISA, Western blot and qRT-PCR, respectively. Transepithelial electrical resistance (TEER) assay was conducted to value the barrier function of intestinal mucosa. Cell autophagy and NF-κB and p38MAPK pathways associated proteins were examined through Western blot. In the absence of TNF-α treatment, cell viability and apoptosis showed no significant change. TNF-α decreased cell viability and increased cell apoptosis and BIF treatment mitigated the TNF-α-induced change. Then, we found that BIF treatment effectively suppressed TNF-α-induced overexpression of IL-6 and IL-8. Besides, the results of TEER assay showed that barrier function of intestinal mucosa which was destroyed by TNF-α was effectively recovered by BIF treatment. In addition, TNF-α induced autophagy was also suppressed by BIF. Moreover, TNF-α activated NF-κB and p38MAPK signal pathways were also blocked by BIF, SN50 and SB203580. Our present study reveals that BIF plays a protective role in TNF-α-induced inflammatory response in Caco-2 cells through NF-κB and p38MAPK pathways.
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Affiliation(s)
- Nana Nie
- Department of Pediatric Cardiology, Nephrology and Rheumatology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Cui Bai
- Department of Pediatric Cardiology, Nephrology and Rheumatology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Shanai Song
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Yanyan Zhang
- Department of Neonatal Intensive Care Unit, Qingdao Women and Children's Hospital, No. 6 Tongfu Road, Shibei District, Qingdao, 266034, China
| | - Benzhen Wang
- Heart Center, Qingdao Women and Children's Hospital, No. 6 Tongfu Road, Shibei District, Qingdao, 266034, China
| | - Zipu Li
- Heart Center, Qingdao Women and Children's Hospital, No. 6 Tongfu Road, Shibei District, Qingdao, 266034, China.
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Alard J, Peucelle V, Boutillier D, Breton J, Kuylle S, Pot B, Holowacz S, Grangette C. New probiotic strains for inflammatory bowel disease management identified by combining in vitro and in vivo approaches. Benef Microbes 2018; 9:317-331. [PMID: 29488412 DOI: 10.3920/bm2017.0097] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Alterations in the gut microbiota composition play a key role in the development of chronic diseases such as inflammatory bowel disease (IBD). The potential use of probiotics therefore gained attention, although outcomes were sometimes conflicting and results largely strain-dependent. The present study aimed to identify new probiotic strains that have a high potential for the management of this type of pathologies. Strains were selected from a large collection by combining different in vitro and in vivo approaches, addressing both anti-inflammatory potential and ability to improve the gut barrier function. We identified six strains with an interesting anti-inflammatory profile on peripheral blood mononuclear cells and with the ability to restore the gut barrier using a gut permeability model based on Caco-2 cells sensitized with hydrogen peroxide. The in vivo evaluation in two 2,4,6-trinitrobenzene sulfonic acid-induced murine models of colitis highlighted that some of the strains exhibited beneficial activities against acute colitis while others improved chronic colitis. Bifidobacterium bifidum PI22, the strain that exhibited the most protective capacities against acute colitis was only slightly efficacious against chronic colitis, while Bifidobacterium lactis LA804 which was less efficacious in the acute model was the most protective against chronic colitis. Lactobacillus helveticus PI5 was not anti-inflammatory in vitro but the best in strengthening the epithelial barrier and as such able to significantly dampen murine acute colitis. Interestingly, Lactobacillus salivarius LA307 protected mice significantly against both types of colitis. This work provides crucial clues for selecting the best strains for more efficacious therapeutic approaches in the management of chronic inflammatory diseases. The strategy employed allowed us to identify four strains with different characteristics and a high potential for the management of inflammatory diseases, such as IBD.
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Affiliation(s)
- J Alard
- 1 Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL, Centre d'Infection et d'Immunité de Lille, 59000 Lille, France
| | - V Peucelle
- 1 Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL, Centre d'Infection et d'Immunité de Lille, 59000 Lille, France
| | - D Boutillier
- 1 Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL, Centre d'Infection et d'Immunité de Lille, 59000 Lille, France
| | - J Breton
- 1 Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL, Centre d'Infection et d'Immunité de Lille, 59000 Lille, France
| | - S Kuylle
- 2 GENIBIO, Le Pradas, ZI du Couserans, 09190 Lorp-Sentaraille, France
| | - B Pot
- 1 Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL, Centre d'Infection et d'Immunité de Lille, 59000 Lille, France
| | - S Holowacz
- 3 PiLeJe Laboratoire, 37 Quai de Grenelle, 75015 Paris, France
| | - C Grangette
- 1 Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL, Centre d'Infection et d'Immunité de Lille, 59000 Lille, France
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Katsanos KH, Papadakis KA. Inflammatory Bowel Disease: Updates on Molecular Targets for Biologics. Gut Liver 2018; 11:455-463. [PMID: 28486793 PMCID: PMC5491079 DOI: 10.5009/gnl16308] [Citation(s) in RCA: 113] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2016] [Revised: 08/03/2016] [Accepted: 08/03/2016] [Indexed: 12/13/2022] Open
Abstract
Therapy for inflammatory bowel disease (IBD) has changed, with several new agents being evaluated. The era of anti-tumor necrosis factor (anti-TNF) antibody therapy saw remarkable progress in IBD therapy. Some patients, however, do not respond to anti-TNF treatment, or their response decreases over time. This phenomenon highlights the need to identify new molecular targets for therapy in IBD. The targets of new therapeutic molecules in IBD must aim to restore immune dysregulation by the inhibition of proinflammatory cytokines (TNF-α, interleukin [IL]-6, IL-13, IL-17, IL-18, and IL-21) and augmentation of the effect of anti-inflammatory cytokines (IL-10, IL-11, and transforming growth factor β) and to pursue new anti-inflammatory targets, such as regulatory T-cell therapy, Smad7 antisense, Janus-activated kinase inhibition, Toll-like receptor stimulation, leukocyte adhesion, and blockade of T-cell homing via integrins and mucosal addressin cellular adhesion molecule-1. In addition, potential molecular targets could restore mucosal barrier function and stimulate mucosal healing. Despite these potential targets, the value and clinical significance of most new molecules remain unclear, and clinical efficacy and safety must be better defined before their implementation in clinical practice. This article aims to review the promising and emerging molecular targets that could be clinically meaningful for novel therapeutic approaches.
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Affiliation(s)
- Konstantinos H Katsanos
- Division of Gastroenterology, Department of Internal Medicine, University of Ioannina School of Health Sciences, Ioannina, Greece
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8
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Patten DA, Hussein E, Davies SP, Humphreys PN, Collett A. Commensal-derived OMVs elicit a mild proinflammatory response in intestinal epithelial cells. MICROBIOLOGY-SGM 2017; 163:702-711. [PMID: 28530169 DOI: 10.1099/mic.0.000468] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Under normal physiological conditions, the intestinal immunity remains largely hyporesponsive to the commensal microbiota, yet also retains the inherent ability to rapidly respond to pathogenic antigens. However, immunomodulatory activities of extracellular products from commensal bacteria have been little studied, with previous investigations generally utilizing the live bacterium to study microbiota-epithelial interactions. In this study, we demonstrate that extracellular products of a commensal bacterium, Escherichia coli C25, elicit a moderate release of proinflammatory IL-8 and stimulate transcriptional up-regulation of Toll-like receptors (TLRs) in intestinal epithelial cell lines HT29-19A and Caco-2. Additionally, we show that removal of outer membrane vesicles (OMVs) reduces the proinflammatory effect of secreted products from E. coli C25. Furthermore, we show that isolated OMVs have a dose-dependent proinflammatory effect on intestinal epithelial cells (IECs). Interestingly, a relatively high concentration (40 µg ml-1 protein) of OMVs had no significant regulatory effects on TLR mRNA expression in both cell lines. Finally, we also demonstrate that pre-incubation with E. coli C25-derived OMVs subsequently inhibited the internalization of the bacterium itself in both cell lines. Taken together, our results suggest that commensal-derived extracellular products, in particular OMVs, could significantly contribute to intestinal homeostasis. We also demonstrate a unique interaction between commensal-derived OMVs and host cells.
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Affiliation(s)
- Daniel A Patten
- Department of Chemical and Biological Sciences, University of Huddersfield, Huddersfield, UK.,Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Enas Hussein
- Department of Chemical and Biological Sciences, University of Huddersfield, Huddersfield, UK
| | - Scott P Davies
- Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Paul N Humphreys
- Department of Chemical and Biological Sciences, University of Huddersfield, Huddersfield, UK
| | - Andrew Collett
- Department of Chemical and Biological Sciences, University of Huddersfield, Huddersfield, UK
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9
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Chung MY, Hwang JT, Kim JH, Shon DH, Kim HK. Sarcodon aspratus Extract Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mouse Colon and Mesenteric Lymph Nodes. J Food Sci 2016; 81:H1301-8. [PMID: 27074537 DOI: 10.1111/1750-3841.13297] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Revised: 03/03/2016] [Accepted: 03/14/2016] [Indexed: 12/19/2022]
Abstract
Mushrooms have been previously investigated for their immune-modulating and anti-inflammatory properties. We examined whether the anti-inflammatory properties of Sarcodon aspratus ethanol extract (SAE) could elicit protective effects against dextran sulfate sodium (DSS)-induced colitis in vivo. Male C57/BL6 mice were randomly assigned to 1 of 4 treatment groups: control (CON; n = 8), DSS-treated (DSS; n = 9), DSS+SAE at 50 mg/kg BW (SAE50; n = 8), and DSS+SAE at 200 mg/kg BW groups (SAE200; n = 9). DSS treatment induced significant weight loss, which was significantly recovered by SAE200. Although SAE did not affect DSS-mediated reductions in colon length, it improved diarrhea and rectal bleeding induced by DSS. SAE at 200 mg/kg BW significantly attenuated IL-6 and enhanced IL-10 expression in mesenteric lymph nodes (MLN), and significantly reduced IL-6 levels in splenocytes. SAE200 also significantly attenuated DSS-induced increase in IL-6 and IL-1β, and reductions in IL-10 in colon tissue. High levels of SAE were also observed to significantly decrease inflammatory COX-2 expression that was upregulated by DSS in mice colon. These findings may have relevance for novel therapeutic strategies to mitigate inflammatory bowel disease-relevant inflammatory responses, via the direct and indirect anti-inflammatory activity of SAE. We also found that SAE harbors significant quantities of total fiber and β-glucan, suggesting a possible role for these components in protection against DSS-mediated colitis.
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Affiliation(s)
- Min-Yu Chung
- Div. of Nutrition and Metabolism Research, Korea Food Research Inst, Seongnam, Republic of Korea
| | - Jin-Taek Hwang
- Dept. of Food Biotechnology, Korea Univ. of Science & Technology, Daejeon, Republic of Korea
| | - Jin Hee Kim
- Div. of Nutrition and Metabolism Research, Korea Food Research Inst, Seongnam, Republic of Korea
| | - Dong-Hwa Shon
- Div. of Nutrition and Metabolism Research, Korea Food Research Inst, Seongnam, Republic of Korea
| | - Hyun-Ku Kim
- Div. of Nutrition and Metabolism Research, Korea Food Research Inst, Seongnam, Republic of Korea
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10
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Berberine is a dopamine D1- and D2-like receptor antagonist and ameliorates experimentally induced colitis by suppressing innate and adaptive immune responses. J Neuroimmunol 2015; 289:43-55. [DOI: 10.1016/j.jneuroim.2015.10.001] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Revised: 09/24/2015] [Accepted: 10/05/2015] [Indexed: 12/17/2022]
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11
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Tang W, Wang H, Claudio E, Tassi I, Ha HL, Saret S, Siebenlist U. The oncoprotein and transcriptional regulator Bcl-3 governs plasticity and pathogenicity of autoimmune T cells. Immunity 2015; 41:555-66. [PMID: 25367572 DOI: 10.1016/j.immuni.2014.09.017] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2013] [Accepted: 09/10/2014] [Indexed: 02/06/2023]
Abstract
Bcl-3 is an atypical member of the IκB family that modulates transcription in the nucleus via association with p50 (NF-κB1) or p52 (NF-κB2) homodimers. Despite evidence attesting to the overall physiologic importance of Bcl-3, little is known about its cell-specific functions or mechanisms. Here we demonstrate a T-cell-intrinsic function of Bcl-3 in autoimmunity. Bcl-3-deficient T cells failed to induce disease in T cell transfer-induced colitis and experimental autoimmune encephalomyelitis. The protection against disease correlated with a decrease in Th1 cells that produced the cytokines IFN-γ and GM-CSF and an increase in Th17 cells. Although differentiation into Th1 cells was not impaired in the absence of Bcl-3, differentiated Th1 cells converted to less-pathogenic Th17-like cells, in part via mechanisms involving expression of the RORγt transcription factor. Thus, Bcl-3 constrained Th1 cell plasticity and promoted pathogenicity by blocking conversion to Th17-like cells, revealing a unique type of regulation that shapes adaptive immunity.
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Affiliation(s)
- Wanhu Tang
- Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
| | - Hongshan Wang
- Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
| | - Estefania Claudio
- Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
| | - Ilaria Tassi
- Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
| | - Hye-lin Ha
- Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
| | - Sun Saret
- Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
| | - Ulrich Siebenlist
- Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
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12
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Yang X, Yang Y, Wang Y, Zhan B, Gu Y, Cheng Y, Zhu X. Excretory/secretory products from Trichinella spiralis adult worms ameliorate DSS-induced colitis in mice. PLoS One 2014; 9:e96454. [PMID: 24788117 PMCID: PMC4008629 DOI: 10.1371/journal.pone.0096454] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2013] [Accepted: 04/08/2014] [Indexed: 12/19/2022] Open
Abstract
Background Many evidences show the inverse correlation between helminth infection and allergic or autoimmune diseases. Identification and characterization of the active helminth-derived products responsible for the beneficial effects on allergic or inflammatory diseases will provide another feasible approach to treat these diseases. Methods and Findings Colitis was induced in C57BL/6 mice by giving 3% DSS orally for 7 days. During this period, the mice were treated daily with the excretory/secretory products from T. spiralis adult worms (AES) intraperitoneally. The severity of colitis was monitored by measuring body weight, stool consistency or bleeding, colon length and inflammation. To determine the T. spiralis AES product-induced immunological response, Th1, Th2, Th17 and regulatory cytokine profiles were measured in lymphocytes isolated from colon, mesenteric lymph nodes (MLN), and the spleen of treated mice. The CD4+ CD25+ FOXP3+ regulatory T cells (Tregs) were also measured in the spleens and MLN of treated mice. Mice treated with AES significantly ameliorated the severity of the DSS-induced colitis indicated by the reduced disease manifestations, improved macroscopic and microscopic inflammation correlated with the up-regulation of Treg response (increased regulatory cytokines IL-10, TGF-beta and regulatory T cells) and down-regulation of pro-inflammatory cytokines (IFN-gamma, IL-6 and IL-17) in the spleens, MLN and colon of treated mice. Conclusions Our results provide direct evidences that T. spiralis AES have a therapeutic potential for alleviating inflammatory colitis in mice. This effect is possibly mediated by the immunomodulation of regulatory T cells to produce regulatory and anti-inflammatory cytokines and inhibit pro-inflammatory cytokines.
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Affiliation(s)
- Xiaodi Yang
- Department of Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
- Department of Microbiology and Parasitology, Bengbu Medical College; Anhui Key Laboratory of Infection and Immunity, Bengbu, Anhui, China
| | - Yaping Yang
- Department of Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Yunyun Wang
- Department of Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Bin Zhan
- Section of Tropical Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America
| | - Yuan Gu
- Department of Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Yuli Cheng
- Department of Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Xinping Zhu
- Department of Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
- * E-mail:
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Salem M, Seidelin JB, Rogler G, Nielsen OH. Muramyl dipeptide responsive pathways in Crohn's disease: from NOD2 and beyond. Cell Mol Life Sci 2013; 70:3391-404. [PMID: 23275943 PMCID: PMC11113952 DOI: 10.1007/s00018-012-1246-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2012] [Revised: 12/12/2012] [Accepted: 12/13/2012] [Indexed: 12/15/2022]
Abstract
Crohn's disease (CD) is one of main disease entities under the umbrella term chronic inflammatory bowel disease. The etiology of CD involves alterations in genetic, microbiological, and immunological factors. This review is devoted to the role of the bacterial wall compound muramyl dipeptide (MDP) for the activation of inflammatory pathways involved in the pathogenesis of CD. The importance of this molecule is underscored by the fact that (1) MDP, which is found in most Gram-negative and -positive bacteria, is able to trigger several immunological responses in the intestinal system, and (2) that alterations in several mediators of the MDP response including-but not restricted to-nucleotide oligomerization domain 2 (NOD2) are associated with CD. The normalization of MDP signaling is one of several important factors that influence the intestinal inflammatory response, a fact which emphasizes the pathogenic importance of MDP signaling for the pathogenesis of CD. The important aspects of NOD2 and non-NOD2 mediated effects of MDP for the development of CD are highlighted, as well as how alterations in these pathways might translate into the development of new therapeutic strategies.
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Affiliation(s)
- Mohammad Salem
- Department of Gastroenterology D, Medical Section, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, 2730 Herlev, Denmark
| | - Jakob Benedict Seidelin
- Department of Gastroenterology D, Medical Section, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, 2730 Herlev, Denmark
- Department of Internal Medicine, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Gerhard Rogler
- Department of Gastroenterology and Hepatology, Zürich University Hospital, Zurich, Switzerland
| | - Ole Haagen Nielsen
- Department of Gastroenterology D, Medical Section, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, 2730 Herlev, Denmark
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Qian Q, Li P, Wang T, Zhang J, Yu S, Chen T, Yan L, Song Y, Liu X, Gu Y, Wang Y, Jia G. Alteration of Th1/Th2/Th17 cytokine profile and humoral immune responses associated with chromate exposure. Occup Environ Med 2013; 70:697-702. [PMID: 23811143 DOI: 10.1136/oemed-2013-101421] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND The role of chromate exposure in the deregulation of total lymphocyte and other immune factors is largely unclear. OBJECTIVES We aimed to examine alteration of the Th1/Th2/Th17 cytokine profile and humoral indicators caused by occupational chromate exposure. METHODS A cross-sectional study was conducted in two similar workshops (groups 1 and 2) with 106 male occupational workers and 50 matched local controls. Environmental and biological exposures were assessed by measuring chromium concentrations in workplace air, and in whole blood and urine samples of the workers. Cytokines in serum (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, IL-17A) were determined by CBA assay, while immunoglobin (IgA, IgM, IgG, IgE) and complement (C3, C4) were evaluated by immunonephelometric and ELISA methods. Micronucleus analysis was also used to explore the relationship between genotoxicity and immunotoxicity. RESULTS Compared with the control group, environmental chromate exposure in groups 1 and 2 was much higher, and the mean values of IL-6, IL-10, IFN-γ, IL-17A and IFN-γ/IL-4 were significantly decreased in group 1. In group 2, IgA and IgG levels were reduced, while C3 and C4 were increased. Levels of IFN-γ, IgG and IgA were all inversely associated with whole blood chromium, while C3 and C4 were positively associated with whole blood chromium (p<0.05). Both IL-10 and IL-17A were inversely associated with urine chromium. Correlations were also found between IL-10, IL-17A and micronucleus (r=-0.329, r=-0.312, respectively). CONCLUSIONS Occupational exposure to chromate could downregulate the cellular and humoral factors of the immune system.
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Affiliation(s)
- Qin Qian
- Department of Occupational and Environmental Health Science, School of Public Health, Peking University, Beijing, P. R. China
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Accumulation of Mast Cells in the Lesions and Effects of Antiallergic Drugs on the Patients with Inflammatory Bowel Disease. ACTA ACUST UNITED AC 2013. [DOI: 10.1155/2013/714807] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The pathomechanism of inflammatory bowel disease (IBD) has not yet been fully demonstrated. However, it is well known that mast cells are present in the gastrointestinal tract, suggesting that mast cells may take part in it. So, we investigated the number of mast cells in IBD, such as ulcerative colitis (UC) and eosinophilic colitis, and showed that the number of mast cells was increased in the inflammatory lesions. We also presented a case of UC which was treated successfully with an antiallergic drug, tranilast. Furthermore, possible new approaches to treating the disease with immunomodulators including suplatast are introduced. However, our investigations were performed with a limited number of patients with IBD, and additional further studies are required to confirm the findings.
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Azer SA. Overview of molecular pathways in inflammatory bowel disease associated with colorectal cancer development. Eur J Gastroenterol Hepatol 2013; 25:271-281. [PMID: 23169309 DOI: 10.1097/meg.0b013e32835b5803] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Patients with long-standing inflammatory bowel disease (IBD) are at a higher risk of developing colorectal cancer (CRC). This risk increases with the longer duration of colitis, greater extent of inflammation, a family history of CRC, severity of bowel inflammation, and a coexistent primary sclerosing cholangitis. The cornerstone for comprehending the development of CRC in IBD and hence early detection is based on the understanding of the molecular pathways of IBD itself. At a molecular level, the pathogenesis of CRC is related to understanding the inflammatory changes and involves multiple inter-related pathways including (i) genetic alterations (e.g. chromosomal and microsatellite instability and hypermethylation), (ii) mucosal inflammatory mediators (e.g. COX-2, interleukin-6, interleukin-23, tumor necrosis factor-α, nuclear factor-κB, and chemokines), (iii) changes in the expression of receptors on the epithelial cells, and (iv) oxidant stress, mucosal breakdown, and intestinal microbiota. The aim of this review is to provide an evidence-based approach for the role of chronic inflammatory mechanisms and the molecular basis of these mechanisms in the development of CRC. Therefore, understanding the molecular basis of CRC is an important step for the identification of new biomarkers that can help in the early detection of CRC in these patients.
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Affiliation(s)
- Samy A Azer
- Department of Medical Education, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
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Habal F, Huang V. Angioedema associated with Crohn's disease: Response to biologics. World J Gastroenterol 2012; 18:4787-90. [PMID: 23002350 PMCID: PMC3442219 DOI: 10.3748/wjg.v18.i34.4787] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2011] [Revised: 05/31/2012] [Accepted: 06/15/2012] [Indexed: 02/06/2023] Open
Abstract
A 46-year-old female patient with terminal ileum Crohn’s disease and ankylosing spondylitis presented with recurrent angioedema and urticaria. Investigations ruled out hereditary angioedema, and environmental or food allergen triggers. She was diagnosed with chronic idiopathic urticaria with angioedema, and was treated with a trial of intravenous immunoglobulin immunotherapy, danazol, prednisone and hydroxyzine. Due to ongoing bowel and arthritic complaints, she was started on infliximab infusions and within 2 treatments, she had complete resolution of the angioedema and urticaria, as well as of the bowel and arthritic symptoms. Unfortunately she developed allergic reactions to the infliximab and was switched to another anti-tumor necrosis factor (TNF)-α agent, adalimumab. Since then, she has had no further angioedema or urticaria, and her Crohn’s disease has been quiescent. This is the first known case report of chronic idiopathic urticaria with angioedema coexistent with Crohn’s disease that was successfully treated with anti-TNF-α agents.
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