|
1
|
Rahimi-Tari M, Sadeghi AA, Motamedi-Sedeh F, Aminafshar M, Chamani M. Hematological parameters, antioxidant status, and gene expression of γ-INF and IL-1β in vaccinated lambs fed different type of lipids. Trop Anim Health Prod 2023; 55:168. [PMID: 37084030 DOI: 10.1007/s11250-023-03585-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 04/12/2023] [Indexed: 04/22/2023]
Abstract
This study was aimed to evaluate the effects of vegetable oils as calcium salt on immune responses and the expression of immune-related genes in vaccinated lambs. Twenty-four lambs (35 kg body weight, 6 months old) were assigned to four treatments with six replicates in a completely randomized design for 40 days. Four concentrates were formulated in which the calcium salts of palm oil, canola oil, corn oil, and flaxseed oil were used. On day 30 of the experiment, lambs were vaccinated by a dose of foot-and-mouth disease virus. The blood samples were collected from jugular vein 10 days after vaccination. The level of malondialdehyde and the activity of liver enzymes were the highest in lambs receiving corn oil and the lowest in lambs receiving flaxseed oil. The highest lymphocytes and the lowest neutrophil percentages were observed in lambs receiving flaxseed oil. There was a significant difference among treatments for the relative genes expression. Flaxseed oil significantly upregulated interferon-γ and corn oil upregulated interleukin-1β. The highest titer against foot-and-mouth disease virus was related to lambs receiving flaxseed oil, and the lowest titer was related to lambs that received corn oil. Flaxseed oil had more beneficial effects on immune response than other oils.
Collapse
Affiliation(s)
- Morteza Rahimi-Tari
- Department of Animal Science, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Ali Asghar Sadeghi
- Department of Animal Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.
| | - Farahnaz Motamedi-Sedeh
- Nuclear Agriculture Research School, Nuclear Science and Technology Research Institute, AEOI, Karaj, Iran
| | - Mehdi Aminafshar
- Department of Animal Science, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Mohammad Chamani
- Department of Animal Science, Science and Research Branch, Islamic Azad University, Tehran, Iran
| |
Collapse
|
|
2
|
Torky HA, Saad HM, Khaliel SA, Kassih AT, Sabatier JM, Batiha GES, Hetta HF, Elghazaly EM, De Waard M. Isolation and Molecular Characterization of Corynebacterium pseudotuberculosis: Association with Proinflammatory Cytokines in Caseous Lymphadenitis Pyogranulomas. Animals (Basel) 2023; 13:ani13020296. [PMID: 36670836 PMCID: PMC9854522 DOI: 10.3390/ani13020296] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/30/2022] [Accepted: 01/11/2023] [Indexed: 01/18/2023] Open
Abstract
Corynebacterium pseudotuberculosis (C. pseudotuberculosis) is a causative agent of numerous chronic diseases, including caseous lymphadenitis (CLA) in sheep and goats, which has a zoonotic potential in humans in addition to a poor therapeutic response. In this study, out of 120 collected samples, only 12 (10%) were positive for C. pseudotuberculosis by PCR and by intraperitoneal injection of male Guinea pigs and then characterized for antimicrobial susceptibility and its genetic-relatedness by enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR), which showed 2-4 bands ranging from 100 to 3000 bp that can be clustered into four clusters (C1-C4). Despite the serotype biovar 1 only infecting sheep and goats, ERIC-PCR reveals intra-subtyping variation. Examination of affected LNs and organs revealed marked enlargement with either thick creamy green pus or multiple abscesses of variable sizes with a central caseated core surrounded by dense fibrous capsule. A histopathological examination revealed a central necrotic core surrounded by a peripheral mantle of mononuclear cells and a fibrous capsule. Positive immune expression of nuclear factor kappa B (NF-κB/p65) and interleukin-1β (IL-1β) and negative expression of tumor necrosis factor (TNF) in CLA is the first report to our knowledge. Conclusion: In CLA pyogranulomas, IL1β is a more crucial proinflammatory cytokine than TNF in the regulation of C. pseudotuberculosis infection, which is accompanied by marked NF-κB immunoexpression. Therefore, the NF-κB/p65 signaling pathway is involved in the activation of IL1β, and additional immunohistochemical studies are required to determine the various roles of NF-κB/p65 in the inflammatory response within CLA pyogranulomas to control this pathogen.
Collapse
Affiliation(s)
- Helmy A. Torky
- Department of Microbiology, Faculty of Veterinary Medicine, Alexandria University, Abees, Alexandria 21523, Egypt
| | - Hebatallah M. Saad
- Department of Pathology, Faculty of Veterinary Medicine, Matrouh University, Marsa Matruh 51744, Egypt
- Correspondence: (H.M.S.); (M.D.W.)
| | - Samy A. Khaliel
- Department of Microbiology, Faculty of Veterinary Medicine, Alexandria University, Abees, Alexandria 21523, Egypt
| | - Asmaa T. Kassih
- Department of Microbiology, Faculty of Veterinary Medicine, Alexandria University, Abees, Alexandria 21523, Egypt
| | - Jean-Marc Sabatier
- Institut de Neurophysiopathologie (INP), CNRS UMR 7051, Faculté des Sciences Médicales et Paramédicales, Aix-Marseille Université, 27 Bd Jean Moulin, F-13005 Marseille, France
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt
| | - Helal F. Hetta
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Eman M. Elghazaly
- Department of Microbiology, Faculty of Veterinary Medicine, Matrouh University, Marsa Matruh 51744, Egypt
| | - Michel De Waard
- Smartox Biotechnology, 6 Rue des Platanes, F-38120 Saint-Egrève, France
- L’institut Du Thorax, INSERM, CNRS, UNIV NANTES, F-44007 Nantes, France
- LabEx «Ion Channels, Science & Therapeutics», Université de Nice Sophia-Antipolis, F-06560 Valbonne, France
- Correspondence: (H.M.S.); (M.D.W.)
| |
Collapse
|
|
3
|
Lee JK, Choi WS, Song JY, Kwon OS, Lee YJ, Lee JS, Lee S, Choi SR, Lee CH, Lee JY. Anti-inflammatory effects of Athyrium yokoscense extract via inhibition of the Erk1/2 and NF-κB pathways in bisphenol A-stimulated A549 cells. Toxicol Res 2023; 39:135-146. [PMID: 36726827 PMCID: PMC9839918 DOI: 10.1007/s43188-022-00154-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 09/09/2022] [Accepted: 10/12/2022] [Indexed: 11/09/2022] Open
Abstract
Bisphenol A is an environmental endocrine disruptor that has similar functions to estrogen in humans. However, few studies have investigated pulmonary inflammation induced by BPA, and the effect of Athyrium yokoscense extract on this inflammatory response is unknown. In this study, we investigated this effect in A549 human alveolar epithelial cells. BPA at concentrations higher than 100 µM were cytotoxic to A549 cells at 24 and 48 h after treatment; however, AYE (100 µg/mL) had a protective effect against BPA-induced cytotoxicity. AYE also inhibited the generation of intracellular reactive oxygen species, expressions of cyclooxygenase-2 and extracellular signal-regulated kinase1/2 proteins, activities of phospholipase A2, COX-2, nuclear factor kappa-light-chain-enhancer of activated B cells, and proinflammatory mediators including prostaglandin E2, tumor necrosis factor-α, and interleukin-6 induced by BPA in A549 cells. This study demonstrated that BPA, which induces chronic lung disease, causes oxidative stress and inflammatory response in lung epithelial cell line, and found that AYE reduces BPA-induced oxidative stress and inflammatory response by down-regulating the Erk1/2 and NF-κB pathways.
Collapse
Affiliation(s)
- Jung-Kyu Lee
- College of Pharmacy, Chung-Ang University, Seoul, 06974 Republic of Korea
| | - Won Seok Choi
- College of Pharmacy, Chung-Ang University, Seoul, 06974 Republic of Korea
| | - Jin Yong Song
- College of Pharmacy, Chung-Ang University, Seoul, 06974 Republic of Korea
| | - Oh Seong Kwon
- College of Pharmacy, Chung-Ang University, Seoul, 06974 Republic of Korea
| | - Yeon Jin Lee
- College of Pharmacy, Chung-Ang University, Seoul, 06974 Republic of Korea
| | - Jong Seok Lee
- National Institute of Biological Resources, Incheon, 22689 Republic of Korea
| | - Sarah Lee
- National Institute of Biological Resources, Incheon, 22689 Republic of Korea
| | - Se Rin Choi
- Department of Bioscience and Biotechnology, Konkuk University, Seoul, 05029 Republic of Korea
| | - Choong Hwan Lee
- Department of Bioscience and Biotechnology, Konkuk University, Seoul, 05029 Republic of Korea
| | - Ji-Yun Lee
- College of Pharmacy, Chung-Ang University, Seoul, 06974 Republic of Korea
| |
Collapse
|
|
4
|
Protection against Lipopolysaccharide-Induced Endotoxemia by Terrein Is Mediated by Blocking Interleukin-1β and Interleukin-6 Production. Pharmaceuticals (Basel) 2022; 15:ph15111429. [PMID: 36422559 PMCID: PMC9693353 DOI: 10.3390/ph15111429] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 11/17/2022] [Accepted: 11/17/2022] [Indexed: 11/22/2022] Open
Abstract
Terrein is a fungal metabolite and has been known to exert anti-melanogenesis, anti-cancer, and anti-bacterial activities. However, its role in endotoxemia has never been investigated until now. In the present study, we examined the effect of terrein on lipopolysaccharide (LPS)-induced endotoxemia in mice and characterized the potential mechanisms of action. Treatment with terrein increased the survival of mice and decreased the production of inflammatory cytokines, including interleukin-1β (IL-1β) and interleukin-6 (IL-6) in an LPS-induced endotoxemia model. In addition, terrein suppressed the LPS-induced production of IL-1β and IL-6 in RAW 264.7 cells, a murine macrophage-like cell line, and the mRNA expression of IL-1β and IL-6 was also inhibited by terrein in LPS-stimulated RAW 264.7 cells. Further study demonstrated that terrein blocked LPS-induced phosphorylation of p65 subunit of nuclear factor (NF)/κB and the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) was also suppressed by terrein treatment. Collectively, these results suggest that terrein exerts a protective effect again LPS-induced endotoxemia in mice by blocking the production of inflammatory cytokines. Our results also suggest that the anti-inflammatory effect of terrein might be mediated, at least in part, by blocking the activation of NF-κB, JNK, and p38 MAPK signaling pathways.
Collapse
|
|
5
|
Wang L, Zhao M. Suppression of NOD-like receptor protein 3 inflammasome activation and macrophage M1 polarization by hederagenin contributes to attenuation of sepsis-induced acute lung injury in rats. Bioengineered 2022; 13:7262-7276. [PMID: 35266443 PMCID: PMC9208453 DOI: 10.1080/21655979.2022.2047406] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Acute lung injury (ALI) is a major leading cause of death in sepsis patients. Hederagenin (HG), derived from Hedera helix Linné, has anti-inflammatory effects, while its role in sepsis-induced ALI has not been elucidated. In vivo, rats were subjected to cecal ligation and puncture to induce ALI and then treated with HG (12.5, 25, or 50 mg/kg) by gavage. Administration of HG raised survival rate, ameliorated lung injury, and decreased lung wet/dry ratio and inflammatory cell accumulation in bronchoalveloar lavage fluid (BALF) of ALI rats. HG inhibited macrophage polarization toward the M1 phenotype as evidenced by decreased CD86 expression in rat lung tissues. Moreover, HG decreased the secretion of TNF-α, IL-6 and monocyte chemoattractant protein-1 (MCP-1) in BALF and the levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lung tissues. In vitro, phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 macrophages were stimulated with 100 ng/mL lipopolysaccharide. HG treatment inhibited M1 macrophage polarization and the production of M1-related pro-inflammatory mediators (IL-6, MCP-1, iNOS, and COX-2). Mechanistically, HG inhibited NLRP3 inflammasome activation and subsequent release of IL-18 and IL-1β, and suppressed NF-κB signaling pathway both in vivo and in vitro. Notably, HG treatment further emphasized the inhibitory effect of NF-κB inhibitor BAY11-7082 on NLRP3 inflammasome activation and macrophage M1 polarization. Taken together, HG exerts a protective effect against sepsis-induced ALI by reducing the inflammatory response and macrophage M1 polarization, which may involve NF-κB pathway-modulated NLRP3 inflammasome activation.
Collapse
Affiliation(s)
- Lin Wang
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Min Zhao
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| |
Collapse
|
|
6
|
Zhou M, Tang Y, Liao L, Liu M, Deng Y, Zhao X, Li Y. Phillygenin inhibited LPS-induced RAW 264.7 cell inflammation by NF-κB pathway. Eur J Pharmacol 2021; 899:174043. [PMID: 33745957 DOI: 10.1016/j.ejphar.2021.174043] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 03/11/2021] [Accepted: 03/12/2021] [Indexed: 02/06/2023]
Abstract
Inflammation is a common pathological phenomenon when homeostasis is seriously disturbed. Phillygenin (PHI), a lignin component isolated from Forsythiae Fructus, has shown a good anti-inflammatory effect. However, the mechanisms of PHI on anti-inflammation have not yet been systematically elucidated. In this study, the lipopolysaccharide (LPS) - induced RAW264.7 cell inflammation model was established to investigate mechanisms of PHI on inflammation. The effect of PHI on the release of IL-1β and PGE2 inflammatory factors induced by LPS was detected by ELISA, and the mRNA expressions of IL-1β, IL-6 and TNF-α were detected by RT-qPCR. Proteomics studied the signaling pathways that might be affected by PHI and molecular docking technology was subsequently used to study the possible targets on proteomic screened pathways. Western blot was performed ultimately to detect progressive changes in protein expression on the related pathway. Our research showed that PHI significantly inhibited the robust increase of IL-1β and PGE2 and lowered the transcriptional level of inflammatory genes including IL-6, IL-1β and PGE2 in LPS-stimulated RAW264.7 cells. Proteomics results indicated that PHI was involved in the regulation of multiple signaling pathways. Molecular docking results indicated that PHI had an affinity for most proteins in NF-κB pathway. Western blot analysis proved that PHI inhibited LPS-induced NF-κB pathway activation. On the whole, PHI inhibited the activation of NF-κB pathway, thereby inhibiting the expression of related inflammatory genes and the release of cytokines, and showed a remarkable anti-inflammatory effect.
Collapse
Affiliation(s)
- Mengting Zhou
- State Key Laboratory of Southwestern Chinese Medicine Resources; Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Yunqiu Tang
- State Key Laboratory of Southwestern Chinese Medicine Resources; Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Li Liao
- State Key Laboratory of Southwestern Chinese Medicine Resources; Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Meichen Liu
- State Key Laboratory of Southwestern Chinese Medicine Resources; Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Ying Deng
- State Key Laboratory of Southwestern Chinese Medicine Resources; Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Xingtao Zhao
- State Key Laboratory of Southwestern Chinese Medicine Resources; Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Yunxia Li
- State Key Laboratory of Southwestern Chinese Medicine Resources; Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
| |
Collapse
|
|
7
|
Ricardo Carvalho VP, Figueira da Silva J, Buzelin MA, Antônio da Silva Júnior C, Carvalho Dos Santos D, Montijo Diniz D, Binda NS, Borges MH, Senna Guimarães AL, Rita Pereira EM, Gomez MV. Calcium channels blockers toxins attenuate abdominal hyperalgesia and inflammatory response associated with the cerulein-induced acute pancreatitis in rats. Eur J Pharmacol 2021; 891:173672. [PMID: 33190801 DOI: 10.1016/j.ejphar.2020.173672] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 10/20/2020] [Accepted: 10/21/2020] [Indexed: 11/26/2022]
Abstract
Agents that modulate the activity of high-voltage gated calcium channels (HVCCs) exhibit experimentally and clinically significant effect by relieving visceral pain. Among these agents, the toxins Phα1β and ω-conotoxin MVIIA effectively reduce chronic pain in rodent models. The molecular mechanisms underlying the chronic pain associated with acute pancreatitis (AP) are poorly understood. Hypercalcemia is a risk factor; the role of cytosolic calcium is considered to be a modulator of pancreatitis. Blockade of Ca2+ signals may be useful as a prophylactic treatment of pancreatitis. We explored the pathophysiological roles of three peptide toxins: Phα1β and its recombinant form CTK 01512-2-blockers of TRPA1 receptor and HVCCs and ω-conotoxin MVIIA, a specific blocker of N-type calcium channels in cerulein-induced AP. Cerulein injection elicits AP in rats, evidenced by an increase in hyperalgesic pain, inflammatory infiltration, amylase and lipase secretion, and reactive oxygen species, TNF-α, and p65 NF-κB levels. These effects of cerulein-induced AP were abolished by Phα1β and its recombinant form CTK 01512-2, whereas ω-conotoxin MVIIA had no effect on the induced increase in pancreatic enzyme secretion. Our results demonstrate that Phα1β and CTK 01512-2 toxins-antagonists of HVCCs and TRPA1 receptor presented an effective response profile, in the control of nociception and inflammatory process in the AP model in rats, without causing changes in spontaneous locomotion of the rats.
Collapse
Affiliation(s)
| | - Juliana Figueira da Silva
- Nucleo de Pós-graduação, Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brazil
| | - Marcelo Araújo Buzelin
- Nucleo de Pós-graduação, Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brazil
| | | | - Duana Carvalho Dos Santos
- Nucleo de Pós-graduação, Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brazil
| | - Danuza Montijo Diniz
- Nucleo de Pós-graduação, Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brazil
| | - Nancy Scardua Binda
- Laboratório de Farmacologia, Departamento de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil
| | | | - André Luiz Senna Guimarães
- Programa de Pós-graduação em Ciências da Saúde, Universidade Estadual de Montes Claros, Montes Claros, MG, Brazil
| | - Elizete Maria Rita Pereira
- Nucleo de Pós-graduação, Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brazil
| | - Marcus Vinicius Gomez
- Nucleo de Pós-graduação, Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brazil.
| |
Collapse
|
|
8
|
Zhang XP, Zhang WT, Qiu Y, Ju MJ, Yang C, Tu GW, Luo Z. Cyclic helix B peptide alleviates sepsis-induced acute lung injury by downregulating NLRP3 inflammasome activation in alveolar macrophages. Int Immunopharmacol 2020; 88:106849. [PMID: 32795894 DOI: 10.1016/j.intimp.2020.106849] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 07/13/2020] [Accepted: 07/26/2020] [Indexed: 02/07/2023]
Abstract
Acute lung injury (ALI) exhibits high clinical morbidity and mortality rates. Our previous study has indicated that the novel proteolysis-resistant cyclic helix B peptide (CHBP) exerts an anti-inflammatory effect in mice with AKI. In the present study, we evaluated the effect of CHBP in an in vivo sepsis-induced ALI model and in vitro using lipopolysaccharide (LPS) and ATP stimulated bone marrow-derived macrophages (BMDMs). For in vivo experiments, mice were randomly divided into three groups: 1) sham; 2) LPS; and 3) LPS + CHBP (n = 6). All relevant data were collected after 18 h. Following CHBP treatment, the lung function of the mice was significantly improved compared to the LPS group. CHBP administration inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α production at both the protein and mRNA levels. Additionally, following CHBP treatment, the population of pulmonary macrophages decreased. Simultaneously, the proportion of caspase-1-activated alveolar macrophages was also decreased after CHBP treatment. The protein levels of NLRP3 and cleaved caspase-1 were attenuated in the lung tissue following CHBP treatment. In in vitro experiments, CHBP treatment decreased NLRP3 inflammasome expression and downstream IL-1β secretion, consistent with the in vivo results. In addition, CHBP reversed nuclear factor (NF)-κB and I-κB phosphorylation with a significant dose-dependent effect. Therefore, these findings suggest the potential of CHBP as a therapeutic agent in sepsis-induced ALI owing to inhibition of the NLRP3 inflammasome via the NF-κB pathway in macrophages.
Collapse
Affiliation(s)
- Xue-Peng Zhang
- Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai 200032, People's Republic of China
| | - Wei-Tao Zhang
- Department of Urology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai 200032, People's Republic of China; Shanghai Key Laboratory of Organ Transplantation, No. 179 Fenglin Road, Xuhui District, Shanghai 200032, People's Republic of China
| | - Yue Qiu
- Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai 200032, People's Republic of China
| | - Min-Jie Ju
- Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai 200032, People's Republic of China
| | - Cheng Yang
- Department of Urology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai 200032, People's Republic of China; Shanghai Key Laboratory of Organ Transplantation, No. 179 Fenglin Road, Xuhui District, Shanghai 200032, People's Republic of China
| | - Guo-Wei Tu
- Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai 200032, People's Republic of China.
| | - Zhe Luo
- Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai 200032, People's Republic of China; Department of Critical Care Medicine, Xiamen Branch, Zhongshan Hospital, Fudan University, No. 668 Jinghu Road, Huli District, Xiamen 361015, People's Republic of China.
| |
Collapse
|
|
9
|
Abbasifard M, Khorramdelazad H. The bio-mission of interleukin-6 in the pathogenesis of COVID-19: A brief look at potential therapeutic tactics. Life Sci 2020; 257:118097. [PMID: 32679148 PMCID: PMC7361088 DOI: 10.1016/j.lfs.2020.118097] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Revised: 07/09/2020] [Accepted: 07/10/2020] [Indexed: 01/08/2023]
Abstract
Interleukin-6 (IL-6), known as an inflammatory cytokine, can be involved in many innate and adaptive immune responses. The role of IL-6 in the pathogenesis of the novel coronavirus disease 2019 (COVID-19) has recently received much more attention due to the spread of the virus and its pandemic potential. Cytokine storm is among the most critical pathological events in patients affected with coronaviruses (CoVs), i.e., severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and COVID-19, causing inflammation-induced lung injury and also occurring as a result of dysregulation of immune responses to the mentioned viruses. IL-6, along with some other inflammatory cytokines, including IL-1 beta (β), IL-8, and tumor necrosis factor-alpha (TNF-α), as well as inflammatory chemokines, can significantly contribute to, fever, lymphopenia, coagulation, lung injury, and multi-organ failure (MOF). Therefore, researchers are to explore novel approaches to treat the disease through targeting of IL-6 and its receptors based on prior experience of other disorders. In this review article, the latest findings on the role of IL-6 in the pathogenesis of COVID-19, as well as therapeutic perspectives, were summarized and discussed.
Collapse
Affiliation(s)
- Mitra Abbasifard
- Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Internal Medicine, Ali-Ibn-Abi-talib Hospital, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Hossein Khorramdelazad
- Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
10
|
Overexpression of MALAT1 Relates to Lung Injury through Sponging miR-425 and Promoting Cell Apoptosis during ARDS. Can Respir J 2019; 2019:1871394. [PMID: 31871512 PMCID: PMC6913333 DOI: 10.1155/2019/1871394] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2019] [Revised: 08/21/2019] [Accepted: 09/19/2019] [Indexed: 12/14/2022] Open
Abstract
Background Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury during which severe inflammatory responses induce cell apoptosis, necrosis, and fibrosis. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a multiple function long noncoding RNA that was found overexpressed during acute lung injury. However, the roles of MALAT1 in ARDS patients are still unknown. Methods Total RNA was extracted from the plasma, plasma exosome, and peripheral blood mononuclear cells (PBMCs) from 65 ARDS patients and 36 healthy controls. The MALAT1 and six candidate miRNAs levels were detected by qRT-PCR. The interaction between MALAT1 and miR-425 was predicted using a bioinformatics tool and verified by dual luciferase assay. Exosomes from ARDS patients were cultured with A549 and HFL-1 cells to confirm the delivery of miR-425 by exosomes. Cell apoptosis and viability were determined by flow cytometry and MTT assay. Results We found MALAT1 was significantly increased in the ARDS patients' plasma and PBMCs. The MALAT1 level in PBMCs was negatively correlated with exosomal miR-425 level. MALAT1 interacted with miR-425 and protected phosphatase and tensin homolog (PTEN) expression in A549 and HFL-1 cells. Exosomes from ARDS patients delivered less miR-425 into A549 and HFL-1 cells and induced cell apoptosis via upregulating PTEN. Conclusion This study identified increased MALAT1 and decreased miR-425 in ARDS patients and unveiled their roles during the pathogenesis of ARDS.
Collapse
|
|
11
|
Wang S, Luo Q, Zhou Y, Fan P. CLG from Hemp Seed Inhibits LPS-Stimulated Neuroinflammation in BV2 Microglia by Regulating NF-κB and Nrf-2 Pathways. ACS OMEGA 2019; 4:16517-16523. [PMID: 31616830 PMCID: PMC6788062 DOI: 10.1021/acsomega.9b02168] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/13/2019] [Accepted: 09/12/2019] [Indexed: 06/10/2023]
Abstract
The healthy benefits of hemp (Cannabis sativa L.) seed have often been attributed to its oils and proteins. Recent studies reveal that hemp seed phenylpropionamides could also show various bioactivities. Continuation of our study on hemp seed provided a phenylpropionamide, coumaroylaminobutanol glucopyranoside (CLG). This work investigated the neuroprotective effect of CLG and its underlying mechanism using lipopolysaccharide-induced BV2 microglia. Our study demonstrated that CLG increased adenosine monophosphate-activated protein kinase (AMPK) expression, suppressed the nuclear factor-kappa B (NF-κB) signaling pathway by inhibiting the phosphorylation of IκBα and NF-κB p65 and decreased proinflammatory cytokine levels in a concentration-dependent manner. Furthermore, CLG reduced the production of cellular reactive oxygen species and stimulated the nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling pathway. Collectively, these results suggested that CLG effectively and simultaneously inhibited inflammatory responses and oxidative stress through the NF-κB and Nrf-2 signaling pathways. AMPK was also involved in the anti-inflammatory effect of CLG. This study provides new insights into the diverse bioactive constituents of hemp seed.
Collapse
|
|
12
|
Protective Effect of Thymosin β4 against Abdominal Aortic Ischemia-Reperfusion-Induced Acute Lung Injury in Rats. ACTA ACUST UNITED AC 2019; 55:medicina55050187. [PMID: 31121838 PMCID: PMC6572620 DOI: 10.3390/medicina55050187] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Revised: 02/25/2019] [Accepted: 05/17/2019] [Indexed: 12/29/2022]
Abstract
Background and objectives: Ischemia-reperfusion (IR) caused by infrarenal abdominal aorta cross-clamping is an important factor in the development of ischemia-reperfusion injury in various distant organs. Materials and Methods: We investigated potential antioxidant/anti-inflammatory effects of thymosin beta 4 (Tβ4) in a rat model of abdominal aortic surgery-induced IR. Tβ4 (10 mg/kg, intravenous (i.v.)) was administered to rats with IR (90-min ischemia, 180-min reperfusion) at two different periods. One group received Tβ4 1 h before ischemia, and the other received 15 min before the reperfusion period. Results: Results were compared to control and non-Tβ4-treated rats with IR. Serum, bronchoalveolar lavage fluid and lung tissue levels of oxidant parameters were higher, while antioxidant levels were lower in the IR group compared to control. IR also increased inflammatory cytokine levels. Tβ4 reverted these parameters in both Tβ4-treated groups compared to the untreated IR group. Conclusions: Since there is no statistical difference between the prescribed results of both Tβ4-treated groups, our study demonstrates that Tβ4 reduced lung oxidative stress and inflammation following IR and prevented lung tissue injury regardless of timing of administration.
Collapse
|
|
13
|
Effects of SHINBARO2 on Rat Models of Lumbar Spinal Stenosis. Mediators Inflamm 2019; 2019:7651470. [PMID: 31182933 PMCID: PMC6512060 DOI: 10.1155/2019/7651470] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2018] [Revised: 03/20/2019] [Accepted: 03/28/2019] [Indexed: 01/05/2023] Open
Abstract
Lumbar spinal stenosis (LSS) is a major cause of chronic low back pain; however, only a few therapies which have been used in clinics still have limited effects on functional recovery. SHINBARO2 is a refined traditional formulation for inflamed lesions and relieve pain of muscular skeletal disease. This study aimed at investigating the effects of SHINBARO2 on LSS and at determining its underlying molecular mechanism in rat models. The LSS rat models were set up by surgical operations in 6-week-old male Sprague-Dawley rats. SHINBARO2 was orally or intraperitoneally administered for 14 days. The motor and sensory ability of rats were evaluated using the activity cage and hot plate method. On the termination day, total vertebrae including the disc and spinal cord were excised for ex vivo study. SHINBARO2 improved locomotor functions and pain sensitivity in LSS rat models. Mechanism study suggested that SHINBARO2 inhibited the production of nitric oxide and prostaglandin E2 in tissues from LSS-induced rats. SHINBARO2 also suppressed the expression of proinflammatory cytokines including tumor necrosis factor-α and interleukin-1β. The activation of NF-κB by LSS surgery was effectively reduced by SHINBARO2, which coincided with the inhibition of IκB degradation. In addition, brain-derived neurotrophic factor (BDNF), a potent promoter of neurite growth, and its downstream ERK signaling were also regulated by SHINBARO2. These findings suggest that the effect of SHINBARO2 might be associated in part with the anti-inflammation and pain control in LSS rat models.
Collapse
|
|
14
|
Chang CY, Huang IT, Shih HJ, Chang YY, Kao MC, Shih PC, Huang CJ. Cluster of differentiation 14 and toll-like receptor 4 are involved in the anti-inflammatory effects of tyrosol. J Funct Foods 2019. [DOI: 10.1016/j.jff.2018.12.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
|
|
15
|
Puyo CA, Earhart A, Staten N, Prince OA, Haug C, Kollef M, Awad M. Endotracheal intubation results in acute tracheal damage induced by mtDNA/TLR9/NF-κB activity. J Leukoc Biol 2018; 105:577-587. [PMID: 30548974 PMCID: PMC7379990 DOI: 10.1002/jlb.5a0718-254rr] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Revised: 10/19/2018] [Accepted: 11/25/2018] [Indexed: 12/11/2022] Open
Abstract
Tracheitis secondary to placement of an endotracheal tube (ETT) is characterized by neutrophil accumulation in the tracheal lumen, which is generally associated with epithelial damage. Mitochondrial DNA (mtDNA), has been implicated in systemic inflammation and organ dysfunction following trauma; however, less is known about the effects of a foreign body on local trauma and tissue damage. We hypothesized that tracheal damage secondary to the ETT will result in local release of mtDNA at sufficient levels to induce TLR9 and NF‐κB activation. In a swine model we compared the differences between uncoated, and chloroquine (CQ) and N‐acetylcysteine (NAC) coated ETTs as measured by tracheal lavage fluids (TLF) over a period of 6 h. The swine model allowed us to recreate human conditions. ETT presence was characterized by neutrophil activation, necrosis, and release of proinflammatory cytokines mediated by TLR9/NF‐κB induction. Amelioration of the tracheal damage was observed in the CQ and NAC coated ETT group as shown in tracheal tissue specimens and TLF. The role of TLR9/NF‐κB dependent activity was confirmed by HEK‐Blue hTLR9 reporter cell line analysis after coincubation with TLF specimens with predetermined concentrations of NAC or CQ alone or TLR9 inhibitory oligodeoxynucleotide (iODN). These findings indicate that therapeutic interventions aimed at preventing mtDNA/TLR9/NF‐κB activity may have benefits in prevention of acute tracheal damage.
Collapse
Affiliation(s)
- Carlos A Puyo
- Departments of Anesthesiology and Critical Care, Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA
| | - Alexander Earhart
- Departments of Anesthesiology and Critical Care, Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA
| | - Nicholas Staten
- Departments of Anesthesiology and Critical Care, Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA
| | - Oliver A Prince
- Departments of Anesthesiology and Critical Care, Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA
| | - Colleen Haug
- Departments of Anesthesiology and Critical Care, Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA
| | - Marin Kollef
- Internal Medicine, Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA
| | - Michael Awad
- Surgery, Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA
| |
Collapse
|
|
16
|
Ubale RV, Shastri PN, Oettinger C, D’Souza MJ. Pulmonary Administration of Microparticulate Antisense Oligonucleotide (ASO) for the Treatment of Lung Inflammation. AAPS PharmSciTech 2018; 19:1908-1919. [PMID: 29663290 DOI: 10.1208/s12249-018-1002-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Accepted: 03/19/2018] [Indexed: 01/01/2023] Open
Abstract
Targeted delivery to the lung for controlling lung inflammation is an area that we have explored in this study. The purpose was to use microparticles containing an antisense oligonucleotide (ASO) to NF-κB to inhibit the production of proinflammatory cytokines. Microparticles were prepared using the B-290 Buchi Spray Dryer using albumin as the microparticle matrix. Physicochemical characterization of the microparticles showed the size ranged from 2 to 5 μm, the charge was - 38.4 mV, and they had a sustained release profile over 72 h. Uptake of FITC-labeled ASO-loaded microparticles versus FITC-labeled ASO solution by RAW264.7 murine macrophage cells was 5-10-fold higher. After pulmonary delivery of microparticles to Sprague-Dawley rats, the microparticles were uniformly distributed throughout the lung and were retained in the lungs until 48 h. Serum cytokine (TNF-α and IL-1β) levels of rats after induction of lung inflammation by lipopolysaccharide were measured until 72 h. Animals receiving ASO-loaded microparticles were successful in significantly controlling lung inflammation during this period as compared to animals receiving no treatment. This study was successful in proving that microparticulate ASO therapy was capable of controlling lung inflammation.
Collapse
|
|
17
|
Abstract
PURPOSE OF REVIEW To review the difficult syndrome of catastrophic antiphospholipid syndrome, emphasizing new developments in the diagnosis, pathogenesis and treatment. RECENT FINDINGS Few recent publications directly address pediatric catastrophic antiphospholipid syndrome (CAPS). Most articles are case reports or are data from adult and pediatric registries. The major factors contributing to most pediatric catastrophic antiphospholipid syndrome include infection and the presence of antiphospholipid antibodies, but complement activation also is important in creating diffuse thrombosis in the microcirculation. Treatment of the acute emergency requires anticoagulation, suppression of the hyperinflammatory state and elimination of the triggering infection. Inhibition of complement activation appears to improve outcome in limited studies, and suppression of antiphospholipid antibody formation may be important in long-term management. SUMMARY CAPS, an antibody-mediated diffuse thrombotic disease of microvasculature, is rare in childhood but has high mortality (33-50%). It requires prompt recognition and aggressive multimodality treatment, including anticoagulation, anti-inflammatory therapy and elimination of inciting infection and pathogenic autoantibodies.
Collapse
|
|
18
|
Cavaleri F. Presenting a New Standard Drug Model for Turmeric and Its Prized Extract, Curcumin. Int J Inflam 2018; 2018:5023429. [PMID: 29568482 PMCID: PMC5820622 DOI: 10.1155/2018/5023429] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Accepted: 12/06/2017] [Indexed: 02/07/2023] Open
Abstract
Various parts of the turmeric plant have been used as medicinal treatment for various conditions from ulcers and arthritis to cardiovascular disease and neuroinflammation. The rhizome's curcumin extract is the most studied active constituent, which exhibits an expansive polypharmacology with influence on many key inflammatory markers. Despite the expansive reports of curcucmin's therapeutic value, clinical reliability and research repeatability with curcumin treatment are still poor. The pharmacology must be better understood and reliably mapped if curcumin is to be accepted and used in modern medical applications. Although the polypharmacology of this extract has been considered, in mainstream medicine, to be a drawback, a perspective change reveals a comprehensive and even synergistic shaping of the NF-kB pathway, including transactivation. Much of the inconsistent research data and unreliable clinical outcomes may be due to a lack of standardization which also pervades research standard samples. The possibility of other well-known curcumin by-products contributing in the polypharmacology is also discussed. A new flowchart of crosstalk in transduction pathways that lead to shaping of nuclear NF-kB transactivation is generated and a new calibration or standardization protocol for the extract is proposed which could lead to more consistent data extraction and improved reliability in therapy.
Collapse
Affiliation(s)
- Franco Cavaleri
- Biologic Pharmamedical Research, 688-2397 King George Blvd., White Rock, BC, Canada V4A7E9
| |
Collapse
|
|
19
|
Song H, Park J, Bui PTC, Choi K, Gye MC, Hong YC, Kim JH, Lee YJ. Bisphenol A induces COX-2 through the mitogen-activated protein kinase pathway and is associated with levels of inflammation-related markers in elderly populations. ENVIRONMENTAL RESEARCH 2017; 158:490-498. [PMID: 28709031 DOI: 10.1016/j.envres.2017.07.005] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2017] [Revised: 06/30/2017] [Accepted: 07/03/2017] [Indexed: 05/20/2023]
Abstract
Bisphenol A (BPA) is a well-known endocrine-disrupting chemical, and it is one of the highest volume chemicals produced worldwide. Even though several in vivo and in vitro studies showed positive associations of BPA exposure with pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin (IL)-6, the mechanism by which BPA induces inflammation is unclear. We investigated the mechanism by which BPA induces inflammation (expression of inflammation-related genes, changes in oxidative stress, and cell proliferation and migration) and evaluated the effect of BPA exposure on inflammation-related markers in epidemiologic studies using repeat urine and serum samples from elderly subjects. BPA induced COX-2 expression via nuclear translocation of NF-κB and activation of mitogen-activated protein kinase (MAPK) by phosphorylation of ERK1/2 and enhanced the migration of lung cancer A549 and breast cancer MDAMB-231 cells. In two epidemiologic studies, we detected associations of BPA with six inflammation-related markers (WBC, CRP, IL-10, ALT, AST, and γ-GTP levels). Our findings probably suggest that BPA exposure induces inflammation and exacerbates tumorigenesis.
Collapse
Affiliation(s)
- Heewon Song
- Department of Integrative Bioscience and Biotechnology, College of Life Science, Sejong University, Kwangjin-gu, Seoul 05006, Republic of Korea
| | - Joonwoo Park
- Department of Integrative Bioscience and Biotechnology, College of Life Science, Sejong University, Kwangjin-gu, Seoul 05006, Republic of Korea
| | - Phuong T C Bui
- Department of Integrative Bioscience and Biotechnology, College of Life Science, Sejong University, Kwangjin-gu, Seoul 05006, Republic of Korea
| | - KeunOh Choi
- Department of Integrative Bioscience and Biotechnology, College of Life Science, Sejong University, Kwangjin-gu, Seoul 05006, Republic of Korea
| | - Myung Chan Gye
- Department of Life Science, Hanyang University, Seoul 04763, Republic of Korea
| | - Yun-Chul Hong
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea
| | - Jin Hee Kim
- Department of Integrative Bioscience and Biotechnology, College of Life Science, Sejong University, Kwangjin-gu, Seoul 05006, Republic of Korea.
| | - Young Joo Lee
- Department of Integrative Bioscience and Biotechnology, College of Life Science, Sejong University, Kwangjin-gu, Seoul 05006, Republic of Korea.
| |
Collapse
|
|
20
|
Sethi GS, Dharwal V, Naura AS. Poly(ADP-Ribose)Polymerase-1 in Lung Inflammatory Disorders: A Review. Front Immunol 2017; 8:1172. [PMID: 28974953 PMCID: PMC5610677 DOI: 10.3389/fimmu.2017.01172] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2017] [Accepted: 09/04/2017] [Indexed: 12/19/2022] Open
Abstract
Asthma, acute lung injury (ALI), and chronic obstructive pulmonary disease (COPD) are lung inflammatory disorders with a common outcome, that is, difficulty in breathing. Corticosteroids, a class of potent anti-inflammatory drugs, have shown less success in the treatment/management of these disorders, particularly ALI and COPD; thus, alternative therapies are needed. Poly(ADP-ribose)polymerases (PARPs) are the post-translational modifying enzymes with a primary role in DNA repair. During the last two decades, several studies have reported the critical role played by PARPs in a good of inflammatory disorders. In the current review, the studies that address the role of PARPs in asthma, ALI, and COPD have been discussed. Among the different members of the family, PARP-1 emerges as a key player in the orchestration of lung inflammation in asthma and ALI. In addition, PARP activation seems to be associated with the progression of COPD. Furthermore, PARP-14 seems to play a crucial role in asthma. STAT-6 and GATA-3 are reported to be central players in PARP-1-mediated eosinophilic inflammation in asthma. Interestingly, oxidative stress-PARP-1-NF-κB axis appears to be tightly linked with inflammatory response in all three-lung diseases despite their distinct pathophysiologies. The present review sheds light on PARP-1-regulated factors, which may be common or differential players in asthma/ALI/COPD and put forward our prospective for future studies.
Collapse
Affiliation(s)
| | - Vivek Dharwal
- Department of Biochemistry, Panjab University, Chandigarh, India
| | - Amarjit S Naura
- Department of Biochemistry, Panjab University, Chandigarh, India
| |
Collapse
|
|
21
|
Rahim I, Djerdjouri B, Sayed RK, Fernández-Ortiz M, Fernández-Gil B, Hidalgo-Gutiérrez A, López LC, Escames G, Reiter RJ, Acuña-Castroviejo D. Melatonin administration to wild-type mice and nontreated NLRP3 mutant mice share similar inhibition of the inflammatory response during sepsis. J Pineal Res 2017; 63. [PMID: 28370493 DOI: 10.1111/jpi.12410] [Citation(s) in RCA: 88] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 03/24/2017] [Indexed: 12/18/2022]
Abstract
The NLRP3 inflammasome is involved in the innate immune response during inflammation. Moreover, melatonin blunts the NF-κB/NLRP3 connection during sepsis. Thus, we compared the roles of the NLRP3 inflammasome and/or melatonin treatment in the septic response of wild-type and NLRP3-/- mice. Mouse myocardial tissue was used for this purpose. The nuclear turnover of NF-κB was enhanced during sepsis, with an increase in TNFα, iNOS, and pro-IL-1β. The lack of inflammasome in NLRP3-/- mice significantly reduced that response and blunted IL-1β maturation due to the lack of caspase-1. Clock and Bmal1 did not change in both mouse strains, enhancing Chrono expression in mutants. RORα, which positively regulates Bmal1, was enhanced at a similar extend in both mouse strains, whereas the expression of the Bmal1 repressor, Rev-Erbα, increased in WT but was depressed in NLRP3-/- mice. Nampt, transcriptionally controlled by Bmal1, increased in WT mice together with Sirt1, whereas they remained unchanged in NLRP3-/- mice. Melatonin treatment reduced the septic response in a comparable manner as did the lack of NLRP3, but unlike the latter, it normalized the clock genes turnover through the induction of RORα and repression of Rev-Erbα and Per2, leading to enhanced Nampt and Sirt1. The lack of NLRP3 inflammasome converts sepsis to a moderate inflammatory disease and identifies NLRP3 as a main target for the treatment of sepsis. The efficacy of melatonin in counteracting the NLRP3 inflammasome activation further confirms the indoleamine as a useful therapeutic drug against this serious condition.
Collapse
Affiliation(s)
- Ibtissem Rahim
- Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Granada, Spain
- Département de Biologie et Physiologie Cellulaire, Faculté des Sciences de la Nature et de la Vie, Université Blida 1, Blida, Algeria
- Faculté des Sciences Biologiques, Laboratoire de Biologie Cellulaire et Moléculaire, Université des Sciences et de la Technologie Houari Boumediene, Bab-Ezzouar, Algiers, Algeria
| | - Bahia Djerdjouri
- Faculté des Sciences Biologiques, Laboratoire de Biologie Cellulaire et Moléculaire, Université des Sciences et de la Technologie Houari Boumediene, Bab-Ezzouar, Algiers, Algeria
| | - Ramy K Sayed
- Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Granada, Spain
- Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Sohag University, Sohag, Egypt
| | - Marisol Fernández-Ortiz
- Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Granada, Spain
- Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain
| | - Beatriz Fernández-Gil
- Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Granada, Spain
- Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain
| | - Agustín Hidalgo-Gutiérrez
- Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Granada, Spain
- Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain
| | - Luis C López
- Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Granada, Spain
- Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain
- CIBERfes, Ibs.Granada, and UGC de Laboratorios Clínicos, Complejo Hospitalario de Granada, Granada, Spain
| | - Germaine Escames
- Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Granada, Spain
- Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain
- CIBERfes, Ibs.Granada, and UGC de Laboratorios Clínicos, Complejo Hospitalario de Granada, Granada, Spain
| | - Russel J Reiter
- Department of Cell Systems and Anatomy, UT Health, San Antonio, TX, USA
| | - Darío Acuña-Castroviejo
- Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Granada, Spain
- Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain
- CIBERfes, Ibs.Granada, and UGC de Laboratorios Clínicos, Complejo Hospitalario de Granada, Granada, Spain
| |
Collapse
|
|
22
|
Han BH, Lee YJ, Yoon JJ, Choi ES, Namgung S, Jin XJ, Jeong DH, Kang DG, Lee HS. Hwangryunhaedoktang exerts anti-inflammation on LPS-induced NO production by suppressing MAPK and NF-κB activation in RAW264.7 macrophages. JOURNAL OF INTEGRATIVE MEDICINE-JIM 2017; 15:326-336. [DOI: 10.1016/s2095-4964(17)60350-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
|
|
23
|
Combination of Panaxadiol and Panaxatriol Type Saponins and Ophioponins From Shenmai Formula Attenuates Lipopolysaccharide-induced Inflammatory Injury in Cardiac Microvascular Endothelial Cells by Blocking NF-kappa B Pathway. J Cardiovasc Pharmacol 2017; 69:140-146. [DOI: 10.1097/fjc.0000000000000450] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
|
|
24
|
Wang Y, Men M, Xie B, Shan J, Wang C, Liu J, Zheng H, Yang W, Xue S, Guo C. Inhibition of PKR protects against H 2O 2-induced injury on neonatal cardiac myocytes by attenuating apoptosis and inflammation. Sci Rep 2016; 6:38753. [PMID: 27929137 PMCID: PMC5144063 DOI: 10.1038/srep38753] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2016] [Accepted: 11/14/2016] [Indexed: 12/13/2022] Open
Abstract
Reactive oxygenation species (ROS) generated from reperfusion results in cardiac injury through apoptosis and inflammation, while PKR has the ability to promote apoptosis and inflammation. The aim of the study was to investigate whether PKR is involved in hydrogen peroxide (H2O2) induced neonatal cardiac myocytes (NCM) injury. In our study, NCM, when exposed to H2O2, resulted in persistent activation of PKR due to NCM endogenous RNA. Inhibition of PKR by 2-aminopurine (2-AP) or siRNA protected against H2O2 induced apoptosis and injury. To elucidate the mechanism, we revealed that inhibition of PKR alleviated H2O2 induced apoptosis companied by decreased caspase3/7 activity, BAX and caspase-3 expression. We also revealed that inhibition of PKR suppressed H2O2 induced NFκB pathway and NLRP3 activation. Finally, we found ADAR1 mRNA and protein expression were both induced after H2O2 treatment through STAT-2 dependent pathway. By gain and loss of ADAR1 expression, we confirmed ADAR1 modulated PKR activity. Therefore, we concluded inhibition of PKR protected against H2O2-induced injury by attenuating apoptosis and inflammation. A self-preservation mechanism existed in NCM that ADAR1 expression is induced by H2O2 to limit PKR activation simultaneously. These findings identify a novel role for PKR/ADAR1 in myocardial reperfusion injury.
Collapse
Affiliation(s)
- Yongyi Wang
- Department of Cardiovascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Min Men
- Department of endocrinology, Xi'an Central Hospital, Shaanxi, China
| | - Bo Xie
- Department of Cardiovascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jianggui Shan
- Department of Cardiovascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Chengxi Wang
- Department of Cardiovascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jidong Liu
- Department of Cardiovascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Hui Zheng
- Department of Cardiovascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Wengang Yang
- Department of Cardiovascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Song Xue
- Department of Cardiovascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Changfa Guo
- Department of Cardiovascular Surgery, Zhong Shan Hospital, School of Medicine, Fudan University, Shanghai, China
| |
Collapse
|
|
25
|
Yang Y, Li D, Tian Z, Lv J, Sun F, Wang Q, Liu Y, Xia P. Looped limulus anti-lipopolysaccharide derived peptide CLP-19 induces endotoxin tolerance involved inhibition of NF-κB activation. Biochem Biophys Res Commun 2016; 480:486-491. [DOI: 10.1016/j.bbrc.2016.10.080] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Accepted: 10/22/2016] [Indexed: 02/06/2023]
|
|
26
|
Cross AS. Invited review: Endotoxin tolerance — current concepts in historical perspective. ACTA ACUST UNITED AC 2016. [DOI: 10.1177/09680519020080020201] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- Alan S. Cross
- Division of Infectious Diseases, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA,
| |
Collapse
|
|
27
|
Wang H, Zhao J, Xue G, Wang J, Wu J, Wang D, Dong L. Regulatory effect of cytokine-induced neutrophil chemoattractant, epithelial neutrophil-activating peptide 78 and pyrrolidine dithiocarbamate on pulmonary neutrophil aggregation mediated by nuclear factor-κB in lipopolysaccharide-induced acute respiratory distress syndrome mice. Exp Ther Med 2016; 12:1785-1794. [PMID: 27602092 DOI: 10.3892/etm.2016.3520] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2015] [Accepted: 01/15/2016] [Indexed: 12/31/2022] Open
Abstract
In the present study, the regulatory effect of cytokine-induced neutrophil chemoattractant (CINC) and epithelial neutrophil-activating peptide 78 (ENA-78) on pulmonary neutrophil (PMN) accumulation in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) mice, and the therapeutic effect of pyrrolidine dithiocarbamate (PDTC), was investigated. BALB/c mice were divided into control, LPS and PDTC + LPS groups using a random number table. The phosphorylation of nuclear factor-κB (NF-κB) was detected using a western blot, and the mRNA expression levels of CINC were evaluated using reverse transcription-quantitative polymerase chain reaction. The expression of NF-κB, CINC and ENA-78 was detected using immunohistochemistry. The production of interleukin (IL)-8 and IL-10 in serum and broncho-alveolar lavage fluid (BALF) was analyzed using an enzyme-linked immunosorbent assay. The total number of leukocytes and proportion of PMNs in BALF was also determined. Following injection with LPS (20 mg/kg), the expression levels of p-NF-κB, CINC and ENA-78 were increased in lung tissue, and the expression levels of IL-8, IL-10 and the number of PMNs increased in serum and BALF. However, in comparison with the LPS group, the degree of lung injury was reduced in ARDS mice that were treated with PDTC. In addition, the expression level of p-NF-κB and the production of chemokines in lung tissue decreased in ARDS mice that were treated with PDTC, and the number of PMNs in BALF also decreased. In conclusion, the results of the present study suggest that the LPS-induced phosphorylation of NF-κB may result in the synthesis and release of CINC and ENA-78, which induce the accumulation of PMNs in the lung. Therefore, PDTC may be used to reduce the production of chemokines and cytokines, thereby decreasing the activation of PMNs in lung tissue and reducing the damage of lung tissue in ARDS.
Collapse
Affiliation(s)
- Hongman Wang
- Department of Pulmonary Medicine, The Third Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China; Department of Pulmonary Medicine, The Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai, Guangdong 519100, P.R. China; Department of Pulmonary Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Jiping Zhao
- Department of Pulmonary Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Guansheng Xue
- Department of Thoracic Surgery, 205 Hospital of Chinese People's Liberation Army, Jinzhou, Liaoning 121001, P.R. China
| | - Junfei Wang
- Department of Pulmonary Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Jinxiang Wu
- Department of Pulmonary Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Donghui Wang
- Department of Pulmonary Medicine, The Third Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China
| | - Liang Dong
- Department of Pulmonary Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| |
Collapse
|
|
28
|
Abstract
Catastrophic antiphospholipid syndrome is a rapidly progressive life-threatening disease that causes multiple organ thromboses and dysfunction in the presence of antiphospholipid antibodies. A high index of clinical suspicion and careful investigation are required to make an early diagnosis so that treatment with anticoagulation and corticosteroids can be initiated; plasma exchange and/or intravenous immunoglobulins can be added if the life-threatening condition persists. Despite aggressive treatment and intensive care unit management, patients with catastrophic antiphospholipid syndrome have a 48% mortality rate, primarily attributable to cardiopulmonary failure. This article reviews the current information on the etiopathogenesis, clinical manifestations, diagnosis, management, and prognosis of catastrophic antiphospholipid syndrome.
Collapse
Affiliation(s)
- Setu K Vora
- Pulmonary Physicians of Norwich, Norwich, Connecticut, USA
| | | | | |
Collapse
|
|
29
|
Abstract
The systemic inflammatory response syndrome (SIRS) describes the clinical presentation of patients with systemic activation of the inflammatory response from any underlying cause. SIRS is a common problem in acute medical and surgical practice and an important cause of morbidity and mortality. As a consequence of SIRS, patients may develop multiple organ dysfunction syndrome and acute respiratory distress syndrome (ARDS). Over the recent years our understanding of the inflammatory response in SIRS has increased, but as yet specific immunomodulatory therapies have not proved useful. The mainstay of treatment for patients with SIRS and ARDS remains a general supportive care. It is in this area that more encouraging advances are being made, particularly in the management of invasive ventilation and nutrition. In this review we summarize the definitions, epidemiology and pathophysiology of SIRS, ARDS and related conditions. We then give a description of the clinical consequences and treatment of SIRS and ARDS with an emphasis on current aspects of supportive care.
Collapse
Affiliation(s)
- Hanif Meeran
- Department of Intensive Care, London Chest Hospital, London, UK.,
| | - Mark Messent
- Department of Intensive Care, London Chest Hospital, London, UK
| |
Collapse
|
|
30
|
Carvalho-Filho PC, Gomes-Filho IS, Meyer R, Olczak T, Xavier MT, Trindade SC. Role of Porphyromonas gingivalis HmuY in Immunopathogenesis of Chronic Periodontitis. Mediators Inflamm 2016; 2016:7465852. [PMID: 27403039 PMCID: PMC4925967 DOI: 10.1155/2016/7465852] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2016] [Accepted: 05/25/2016] [Indexed: 12/03/2022] Open
Abstract
Periodontitis is a multifactorial disease, with participation of bacterial, environmental, and host factors. It results from synergistic and dysbiotic multispecies microorganisms, critical "keystone pathogens," affecting the whole bacterial community. The purpose of this study was to review the role of Porphyromonas gingivalis in the immunopathogenesis of chronic periodontitis, with special attention paid to HmuY. The host response during periodontitis involves the innate and adaptive immune system, leading to chronic inflammation and progressive destruction of tooth-supporting tissues. In this proinflammatory process, the ability of P. gingivalis to evade the host immune response and access nutrients in the microenvironment is directly related to its survival, proliferation, and infection. Furthermore, heme is an essential nutrient for development of these bacteria, and HmuY is responsible for its capture from host heme-binding proteins. The inflammatory potential of P. gingivalis HmuY has been shown, including induction of high levels of proinflammatory cytokines and CCL2, decreased levels of IL-8, and increased levels of anti-HmuY IgG and IgG1 antibodies in individuals with chronic periodontitis. Therefore, the HmuY protein might be a promising target for therapeutic strategies and for development of diagnostic methods in chronic periodontitis, especially in the case of patients with chronic periodontitis not responding to treatment, monitoring, and maintenance therapy.
Collapse
Affiliation(s)
- P. C. Carvalho-Filho
- Odontology Course, Bahiana School of Medicine and Public Health, 41150-100 Salvador, BA, Brazil
| | - I. S. Gomes-Filho
- Department of Periodontics, Feira de Santana State University, 44036-900 Feira de Santana, BA, Brazil
| | - R. Meyer
- Department of Biointeraction, Federal University of Bahia, 40110-100 Salvador, BA, Brazil
| | - T. Olczak
- Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland
| | - M. T. Xavier
- Odontology Course, Bahiana School of Medicine and Public Health, 41150-100 Salvador, BA, Brazil
| | - S. C. Trindade
- Department of Periodontics, Feira de Santana State University, 44036-900 Feira de Santana, BA, Brazil
| |
Collapse
|
|
31
|
Chen YL, Chang YY, Kao MC, Huang CJ. Vasopressin inhibits mitogen-activated protein kinases and activated protein-1 in macrophages. ACTA ACUST UNITED AC 2015. [DOI: 10.1016/j.aat.2015.06.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
|
|
32
|
Park J, Eo EY, Lee KH, Park JS, Lee JH, Yoo CG, Lee CT, Cho YJ. The Anti-Inflammatory Effect of Arginine-Vasopressin on Lipopolysaccharide-Induced IκBα/Nuclear Factor-κB Cascade. Korean J Crit Care Med 2015. [DOI: 10.4266/kjccm.2015.30.3.151] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
|
|
33
|
Qu L, Ji Y, Zhu X, Zheng X. hCINAP negatively regulates NF-κB signaling by recruiting the phosphatase PP1 to deactivate IKK complex. J Mol Cell Biol 2015; 7:529-42. [PMID: 26089539 DOI: 10.1093/jmcb/mjv041] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2014] [Accepted: 03/27/2015] [Indexed: 01/26/2023] Open
Abstract
Tight regulation of nuclear factor-κB (NF-κB) signaling is essential to maintain homeostasis in immune system in response to various stimuli, which has been studied extensively and deeply. However, the molecular mechanisms responsible for its negative regulation are not completely understood. Here we demonstrate that human coilin-interacting nuclear ATPase protein (hCINAP) is a novel negative regulator in NF-κB signaling by deactivating IκB kinase (IKK) complex. In response to TNF stimulation, hCINAP dynamically associates with IKKα and IKKβ and inhibits IKK phosphorylation. Notably, hCINAP directly interacts with the catalytic subunits of protein phosphatase 1 (PP1) and mediates the formation of IKK-hCINAP-PP1 complex, serving as an adaptor protein that recruits PP1 to dephosphorylate IKK. Furthermore, decreased levels of hCINAP are observed in several inflammatory diseases with NF-κB hyperactivity. Our study suggests a novel mechanism underlying deactivation of IKK and provides new insight into the negative regulation of NF-κB signaling.
Collapse
Affiliation(s)
- Linglong Qu
- State Key Lab of Protein and Plant Gene Research, Beijing 100871, China Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Beijing 100871, China
| | - Yapeng Ji
- State Key Lab of Protein and Plant Gene Research, Beijing 100871, China Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Beijing 100871, China
| | - Xi Zhu
- Department of Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China
| | - Xiaofeng Zheng
- State Key Lab of Protein and Plant Gene Research, Beijing 100871, China Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Beijing 100871, China
| |
Collapse
|
|
34
|
Yang W, Yue Z, Cui X, Guo Y, Zhang L, Zhou H, Li W. Comparison of the effects of moderate and severe hypercapnic acidosis on ventilation-induced lung injury. BMC Anesthesiol 2015; 15:67. [PMID: 25924944 PMCID: PMC4443663 DOI: 10.1186/s12871-015-0050-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2014] [Accepted: 04/22/2015] [Indexed: 01/12/2023] Open
Abstract
Background We have proved that hypercapnic acidosis (a PaCO2 of 80-100 mmHg) protects against ventilator-induced lung injury in rats. However, there remains uncertainty regarding the appropriate target PaCO2 or if greater CO2 “doses” (PaCO2 > 100 mmHg) demonstrate this effect. We wished to determine whether severe acute hypercapnic acidosis can reduce stretch-induced injury, as well as the role of nuclear factor-κB (NF-κB) in the effects of acute hypercapnic acidosis. Methods Fifty-four rats were ventilated for 4 hours with a pressure-controlled ventilation mode set at a peak inspiratory pressure (PIP) of 30 cmH2O. A gas mixture of carbon dioxide with oxygen (FiCO2 = 4-5%, FiCO2 = 11-12% or FiCO2 = 16-17%; FiO2 = 0.7; balance N2) was immediately administered to maintain the target PaCO2 in the NC (a PaCO2 of 35-45 mmHg), MHA (a PaCO2 of 80-100 mmHg) and SHA (a PaCO2 of 130-150 mmHg) groups. Nine normal or non-ventilated rats served as controls. The hemodynamics, gas exchange and inflammatory parameters were measured. The role of NF-κB pathway in hypercapnic acidosis-mediated protection from high-pressure stretch injury was then determined. Results In the NC group, high-pressure ventilation resulted in a decrease in PaO2/FiO2 from 415.6 (37.1) mmHg to 179.1 (23.5) mmHg (p < 0.001), but improved by MHA (379.9 ± 34.5 mmHg) and SHA (298.6 ± 35.3 mmHg). The lung injury score in the SHA group (7.8 ± 1.6) was lower than the NC group (11.8 ± 2.3, P < 0.05) but was higher than the MHA group (4.4 ± 1.3, P < 0.05). Compared with the NC group, after 4 h of high pressure ventilation, the MHA and SHA groups had decreases in MPO activity of 67% and 33%, respectively, and also declined the levels of TNF-α (58% versus 72%) and MIP-2 (76% versus 60%) in the BALF. Additionally, both hypercapnic acidosis groups reduced stretch–induced NF-κB activation (p < 0.05) and significantly decreased lung ICAM-1 expression (p < 0.05). Conclusions Moderate hypercapnic acidosis (PaCO2 maintained at 80-100 mmHg) has a greater protective effect on high-pressure ventilation-induced inflammatory injury. The potential mechanisms may involve alterations in NF-κB activity.
Collapse
Affiliation(s)
- Wanchao Yang
- Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University; Anesthesiology Key Laboratory, Harbin Medical University, Harbin, 150086, China. .,Education Department of Heilongjiang Province, Anesthesiology Key Laboratory, Harbin Medical University, Harbin, Heilongjiang Province, China.
| | - Ziyong Yue
- Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University; Anesthesiology Key Laboratory, Harbin Medical University, Harbin, 150086, China. .,Education Department of Heilongjiang Province, Anesthesiology Key Laboratory, Harbin Medical University, Harbin, Heilongjiang Province, China.
| | - Xiaoguang Cui
- Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University; Anesthesiology Key Laboratory, Harbin Medical University, Harbin, 150086, China. .,Education Department of Heilongjiang Province, Anesthesiology Key Laboratory, Harbin Medical University, Harbin, Heilongjiang Province, China.
| | - Yueping Guo
- Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University; Anesthesiology Key Laboratory, Harbin Medical University, Harbin, 150086, China. .,Education Department of Heilongjiang Province, Anesthesiology Key Laboratory, Harbin Medical University, Harbin, Heilongjiang Province, China.
| | - Lili Zhang
- Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University; Anesthesiology Key Laboratory, Harbin Medical University, Harbin, 150086, China. .,Education Department of Heilongjiang Province, Anesthesiology Key Laboratory, Harbin Medical University, Harbin, Heilongjiang Province, China.
| | - Huacheng Zhou
- Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University; Anesthesiology Key Laboratory, Harbin Medical University, Harbin, 150086, China. .,Education Department of Heilongjiang Province, Anesthesiology Key Laboratory, Harbin Medical University, Harbin, Heilongjiang Province, China.
| | - Wenzhi Li
- Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University; Anesthesiology Key Laboratory, Harbin Medical University, Harbin, 150086, China.
| |
Collapse
|
|
35
|
Chang YY, Yang CH, Wang SC, Kao MC, Tsai PS, Huang CJ. Vasopressin inhibits endotoxin binding in activated macrophages. J Surg Res 2015; 197:412-8. [PMID: 25979563 DOI: 10.1016/j.jss.2015.04.042] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2014] [Revised: 03/14/2015] [Accepted: 04/14/2015] [Indexed: 10/23/2022]
Abstract
BACKGROUND Vasopressin possesses potent anti-inflammatory effects. Endotoxin recognition (mediated by cluster of differentiation 14 [CD14]), endotoxin binding, and subsequent nuclear factor-κB (NF-κB) activation are essential mechanisms for initiation of the inflammatory response. We elucidated the effects of vasopressin on these essential mechanisms of inflammation with the hypothesis that vasopressin could inhibit CD14 expression, endotoxin binding, and NF-κB activation in activated macrophages. METHODS Murine macrophage-like cell line RAW264.7 cells were stimulated with endotoxin (lipopolysaccharide [LPS]; 100 ng/mL) or LPS plus vasopressin (1000 pg/mL; designated as the LPS and the LPS + V groups, respectively). After reaction, between-group differences in inflammatory molecule concentrations and levels of NF-κB activation, endotoxin-macrophages binding, and CD14 expression were compared. Analysis of variance was performed for statistical analysis. RESULTS The concentrations of chemokine macrophage inflammatory protein 2 and cytokine interleukin 6 of the LPS + V group were significantly lower than those of the LPS group (P = 0.004 and P < 0.001). The nuclear concentration of phosphorylated NF-κB p65 and cytosolic concentration of phosphorylated inhibitor-κBα of the LPS + V group were significantly lower than those of the LPS group (all P < 0.05). In addition, the level of endotoxin-macrophages binding of the LPS + V group was significantly lower than that of the LPS group (P < 0.001). The level of surface CD14 expression of the LPS + V group was also significantly lower than that of the LPS group (P = 0.019). CONCLUSIONS This study confirmed the potent anti-inflammatory effects of vasopressin. The mechanisms underlying the anti-inflammatory effects of vasopressin may involve its effects on inhibiting CD14 expression, endotoxin binding, and subsequent NF-κB activation.
Collapse
Affiliation(s)
- Ya-Ying Chang
- Department of Anesthesiology, Taipei Tzu Chi Hospital, Taipei, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chen-Hsien Yang
- Department of Anesthesiology, Taipei Tzu Chi Hospital, Taipei, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Shih-Ching Wang
- Department of Anesthesiology, Taipei Tzu Chi Hospital, Taipei, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Ming-Chang Kao
- Department of Anesthesiology, Taipei Tzu Chi Hospital, Taipei, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Pei-Shan Tsai
- Graduate Institute of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan
| | - Chun-Jen Huang
- Department of Anesthesiology, Taipei Tzu Chi Hospital, Taipei, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan.
| |
Collapse
|
|
36
|
Zhang X, Li C, Li J, Xu Y, Guan S, Zhao M. Protective effects of protocatechuic acid on acute lung injury induced by lipopolysaccharide in mice via p38MAPK and NF-κB signal pathways. Int Immunopharmacol 2015; 26:229-36. [PMID: 25841318 DOI: 10.1016/j.intimp.2015.03.031] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Revised: 03/06/2015] [Accepted: 03/11/2015] [Indexed: 12/22/2022]
Abstract
The study aims to investigate the effects of protocatechuic acid (PCA) separated from Chinese herbs, on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. The mouse model was induced by intraperitoneal injection of LPS at the dose of 5mg/kg body weight. Three doses of PCA (30, 15, 5 mg/kg) were administered to mice with intraperitoneal injection one hour prior to LPS exposure. Six hours later after LPS administration, the effect of PCA on ALI mice was assessed via histopathological examination by HE staining, inflammatory cytokine production by ELISA assay and RT-PCR, p38MAPK and NF-κB activation by Western blot analysis. We found that PCA administration significantly ameliorated lung histopathological changes and decreased protein concentration in the bronchoalveolar lavage fluid. Furthermore, the overproduction of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was reduced by PCA. Additionally, PCA at the dose of 30 mg/kg could block the activation of p38MAPK and NF-κB signal pathways induced by LPS. In conclusion, our findings demonstrate that PCA possesses a protective effect on LPS-induced ALI in mice via suppression of p38MAPK and NF-κB signal pathways. Therefore, PCA may be useful in the therapy of lung inflammatory diseases, especially for ALI.
Collapse
Affiliation(s)
- Xiuli Zhang
- School of Pharmaceutical Sciences Binzhou Medical University, Yantai, Shandong 264003, China.
| | - Chunli Li
- School of Pharmaceutical Sciences Binzhou Medical University, Yantai, Shandong 264003, China
| | - Jun Li
- School of Pharmaceutical Sciences Binzhou Medical University, Yantai, Shandong 264003, China
| | - Yingzhen Xu
- Stem Cell and Tissue Engineering Laboratory, Dalian University of Technology, Dalian 116024, China
| | - Shui Guan
- Stem Cell and Tissue Engineering Laboratory, Dalian University of Technology, Dalian 116024, China
| | - Mingshan Zhao
- School of Pharmaceutical Sciences Binzhou Medical University, Yantai, Shandong 264003, China
| |
Collapse
|
|
37
|
Liu J, Sun K, Zheng C, Chen X, Zhang W, Wang Z, Shar PA, Xiao W, Wang Y. Pathway as a pharmacological target for herbal medicines: an investigation from reduning injection. PLoS One 2015; 10:e0123109. [PMID: 25830385 PMCID: PMC4382287 DOI: 10.1371/journal.pone.0123109] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2014] [Accepted: 02/27/2015] [Indexed: 12/13/2022] Open
Abstract
As a rich natural resource for drug discovery, Traditional Chinese Medicine (TCM) plays an important role in complementary and alternative medical systems. TCM shows a daunting complexity of compounds featuring multi-components and multi-targets to cure diseases, which thus always makes it extremely difficult to systematically explain the molecular mechanisms adequately using routine methods. In the present work, to reveal the systematic mechanism of herbal formulae, we developed a pathway-based strategy by combining the pathways integrating, target selection, reverse drug targeting and network analysis together, and then exemplified it by Reduning injection (RDN), a clinically widely used herbal medicine injection, in combating inflammation. The anti-inflammatory effects exerted by the major ingredients of RDN at signaling pathways level were systematically investigated. More importantly, our predicted results were also experimentally validated. Our strategy provides a deep understanding of the pharmacological functions of herbal formulae from molecular to systematic level, which may lead to more successful applications of systems pharmacology for drug discovery and development.
Collapse
Affiliation(s)
- Jianling Liu
- College of Life Science, Northwest University, Xi’an, Shaanxi, 710069, China
| | - Ke Sun
- College of Life Science, Northwest University, Xi’an, Shaanxi, 710069, China
- College of Life Science, Northwest A & F University, Yangling, Shaanxi, 712100, China
- Center of Bioinformatics, Northwest A & F University, Yangling, Shaanxi, 712100, China
| | - Chunli Zheng
- College of Life Science, Northwest A & F University, Yangling, Shaanxi, 712100, China
- Center of Bioinformatics, Northwest A & F University, Yangling, Shaanxi, 712100, China
| | - Xuetong Chen
- College of Life Science, Northwest A & F University, Yangling, Shaanxi, 712100, China
- Center of Bioinformatics, Northwest A & F University, Yangling, Shaanxi, 712100, China
| | - Wenjuan Zhang
- College of Life Science, Northwest A & F University, Yangling, Shaanxi, 712100, China
- Center of Bioinformatics, Northwest A & F University, Yangling, Shaanxi, 712100, China
| | - Zhengzhong Wang
- State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Lianyungang, Jiangsu, 222001, China
| | - Piar Ali Shar
- College of Life Science, Northwest A & F University, Yangling, Shaanxi, 712100, China
- Center of Bioinformatics, Northwest A & F University, Yangling, Shaanxi, 712100, China
| | - Wei Xiao
- State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Lianyungang, Jiangsu, 222001, China
- * E-mail: (WX); (YW)
| | - Yonghua Wang
- College of Life Science, Northwest A & F University, Yangling, Shaanxi, 712100, China
- Center of Bioinformatics, Northwest A & F University, Yangling, Shaanxi, 712100, China
- * E-mail: (WX); (YW)
| |
Collapse
|
|
38
|
Kacem M, Simon G, Leschiera R, Misery L, ElFeki A, Lebonvallet N. Antioxidant and anti-inflammatory effects of Ruta chalepensis L. extracts on LPS-stimulated RAW 264.7 cells. In Vitro Cell Dev Biol Anim 2014; 51:128-41. [DOI: 10.1007/s11626-014-9813-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2014] [Accepted: 08/18/2014] [Indexed: 11/24/2022]
|
|
39
|
Zingiber officinale (Ginger): A Future Outlook on Its Potential in Prevention and Treatment of Diabetes and Prediabetic States. ACTA ACUST UNITED AC 2014. [DOI: 10.1155/2014/674684] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Diabetes is reaching pandemic levels in both developing and developed countries and requires safe, affordable, and effective therapies. This report summarises work in our laboratory on the effects of Zingiber officinale (ginger) and its components in diabetes models and provides a future outlook on the potential for their use in type 2 diabetes. A high fat diet rat model showed modulation of body weight gain and normalisation of glucose and lipid metabolic disturbances, with reduction of insulin resistance in a high fat-high carbohydrate diet model. Ginger extract inhibits enhanced NF-κB in liver of high fat-fed rats through inhibition of the IKK/IκBα/NF-κB classical pathway. The major active component (S)-[6]-gingerol inhibited elevated cytokines in inflamed HuH7 cells through suppression of COX2 expression and protection against the ROS pathway. Ginger extract and gingerols enhanced glucose uptake in L6 myotubes, by enhancing translocation of GLUT4 to the surface membrane and activation of AMPKα1 through a Ca2+/calmodulin-dependent protein kinase kinase pathway. (S)-[6]-Gingerol also enhanced energy metabolism through marked increment of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) gene expression and mitochondrial content in L6 skeletal muscle cells. Future studies will require well designed clinical trials on ginger preparations of defined chemical composition.
Collapse
|
|
40
|
Anti-inflammatory activity of baicalein in LPS-stimulated RAW264.7 macrophages via estrogen receptor and NF-κB-dependent pathways. Inflammation 2014; 36:1584-91. [PMID: 23892998 DOI: 10.1007/s10753-013-9703-2] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Baicalein has been used for many years as a popular antiviral and antibacterial in China. Recent investigations revealed that baicalein also has anti-inflammatory activities. Our results indicated that baicalein increases ERE-luciferase activity in an estrogen receptor (ER)-dependent manner when either ERα or ERβ were coexpressed in Hela cells. This study examined whether baicalein exerts an anti-inflammatory effect in RAW264.7 cells through an estrogen receptor-dependent pathway and through regulation of NF-ĸB activation. In lipopolysaccharide (LPS)-induced RAW264.7 cells, baicalein exerts anti-inflammatory effects by inhibiting iNOS, COX-2, and TNF-α mRNA expression; NO production; as well as inflammatory cytokine (IL-1β, PGE2, and TNF-α) production through an ER-dependent pathway. These effects are accompanied with the inhibition of the transcription factor NF-ĸB activation and IκBα phosphorylation. We therefore conclude that baicalein inhibits LPS-induced inflammatory cytokine production via regulation of the NF-ĸB pathway and estrogen-like activity, suggesting that it may be useful for preventing inflammation-related diseases.
Collapse
|
|
41
|
Pyee Y, Chung HJ, Choi TJ, Park HJ, Hong JY, Kim JS, Kang SS, Lee SK. Suppression of inflammatory responses by handelin, a guaianolide dimer from Chrysanthemum boreale, via downregulation of NF-κB signaling and pro-inflammatory cytokine production. JOURNAL OF NATURAL PRODUCTS 2014; 77:917-924. [PMID: 24689881 DOI: 10.1021/np4009877] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
The anti-inflammatory activity of handelin (1), a guaianolide dimer from Chrysanthemum boreale flowers, was evaluated in vivo, and the effects on mediators nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) and the nuclear factor-κB (NF-κB) and ERK/JNK signaling pathways were investigated in vitro. Compound 1 inhibited lipopolysaccharide (LPS)-induced production of NO and PGE2 in cultured mouse macrophage RAW 264.7 cells. The suppression of NO and PGE2 production by 1 was correlated with the downregulation of mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Compound 1 also suppressed the induction of pro-inflammatory cytokines TNF-α and IL-1β in LPS-stimulated RAW 264.7 cells. To further clarify the transcriptional regulatory pathway in the expression of iNOS and COX-2 by 1, the role of NF-κB was determined in RAW 264.7 cells. Compound 1 inhibits the binding activity of NF-κB into the nuclear proteins. The transcriptional activity of NF-κB stimulated with LPS was also suppressed by 1, which coincided with the inhibition of IκB degradation. Compound 1 also suppressed the activation of mitogen-activated protein kinases, including ERK and JNK signaling. In addition, the LPS-stimulated upregulation of miRNA-155 expression was suppressed by 1. The oral administration of 1 inhibited acute inflammation in carrageenan-induced paw and 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema models. The serum level of IL-1β was also inhibited by 1 in a carrageenan-induced paw edema model. These findings suggest that the suppression of NF-κB activation and pro-inflammatory cytokine production may be a plausible mechanism of action for the anti-inflammatory activity of handelin.
Collapse
Affiliation(s)
- Yuna Pyee
- College of Pharmacy, Natural Products Research Institute, Seoul National University , Seoul 151-742, Korea
| | | | | | | | | | | | | | | |
Collapse
|
|
42
|
ZHANG JIANZHENG, LIU ZHI, LIU JIA, REN JIXIN, SUN TIANSHENG. Mitochondrial DNA induces inflammation and increases TLR9/NF-κB expression in lung tissue. Int J Mol Med 2014; 33:817-24. [PMID: 24535292 PMCID: PMC3976143 DOI: 10.3892/ijmm.2014.1650] [Citation(s) in RCA: 171] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2013] [Accepted: 01/30/2014] [Indexed: 12/16/2022] Open
Abstract
Mitochondrial DNA (mtDNA) contains unmethylated CpG motifs that exhibit immune stimulatory capacities. The aim of this study was to investigate whether mtDNA activates the Toll-like receptor 9 (TLR9)/nuclear factor-κB (NF-κB) pathway, thereby contributing to post-traumatic systemic inflammatory response syndrome (SIRS) and lung injury in rats. The effects of mtDNA on macrophage culture were examined in order to elucidate the putative cellular mechanisms. Rats and macrophage cultures were treated with phosphate-buffered saline, nuclear DNA, or mtDNA for 2, 4, 8 and 24 h. Histological analysis of lung tissue was undertaken following hematoxylin and eosin staining, and cytokine levels were assessed by ELISA. NF-κB and IκB-α phosphorylation levels, as well as TLR9 protein expression were determined by western blot analysis; NF-κB, IκB-α and TLR9 mRNA levels were analyzed by RT-PCR. A greater degree of inflammation and lung injury was observed in response to mtDNA. In addition, mtDNA increased serum tumor necrosis factor-α, interleukin (IL)-6 and IL-10 levels in vivo and increased their secretion by cultured macrophages (p<0.05). In lung tissue, mtDNA increased NF-κB, IκB-α and TLR9 mRNA levels (p<0.05); it also increased phosphorylated NF-κB p65 and TLR9 protein levels in the macrophage cultures. Thus, mtDNA may be part of the danger-associated molecular patterns, contributing to the initiation of sterile SIRS through the activation of the TLR9/NF-κB pathway and the induction of pro-inflammatory cytokine production.
Collapse
Affiliation(s)
- JIAN-ZHENG ZHANG
- Department of Orthopedics, Beijing Army General Hospital, Dongcheng, Beijing 100700, P.R. China
| | - ZHI LIU
- Department of Orthopedics, Beijing Army General Hospital, Dongcheng, Beijing 100700, P.R. China
| | - JIA LIU
- Department of Orthopedics, Beijing Army General Hospital, Dongcheng, Beijing 100700, P.R. China
| | - JI-XIN REN
- Department of Orthopedics, Beijing Army General Hospital, Dongcheng, Beijing 100700, P.R. China
| | - TIAN-SHENG SUN
- Department of Orthopedics, Beijing Army General Hospital, Dongcheng, Beijing 100700, P.R. China
| |
Collapse
|
|
43
|
Dirlik M, Karahan A, Canbaz H, Caglikulekci M, Polat A, Tamer L, Aydin S. Effects of sulfasalazine on lipid peroxidation and histologic liver damage in a rat model of obstructive jaundice and obstructive jaundice with lipopolysaccharide-induced sepsis. Curr Ther Res Clin Exp 2014; 70:299-315. [PMID: 24683239 DOI: 10.1016/j.curtheres.2009.08.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/07/2009] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Sulfasalazine, an inhibitor of cyclooxygenase, 5-lipoxygenase, and nuclear factor κB (NF-κB), has been found to alleviate oxidative damage, proinflammatory cytokine production, bile-duct proliferation, neutrophil infiltration, and fibrosis. Therefore, it may have a potential effect in attenuating lipid peroxidation and histologic liver damage in patients with biliary obstruction and biliary obstruction with sepsis. OBJECTIVE The aim of this study was to investigate the effect of sulfasalazine on lipid peroxidation and histologic liver damage due to obstructive jaundice (OJ) and to OJ with lipopolysaccharide (LPS)-induced sepsis in an experimental model. METHODS Male Wistar rats, weighing 150 to 220 g, were randomized into 6 groups: OJ; OJ + LPS; OJ + sulfasalazine; OJ + sulfasalazine + LPS (sulfasalazine administered before sepsis); OJ + LPS + sulfasalazine (sulfasalazine administered after sepsis); and sham. Liver malondialdehyde (MDA) and myeloperoxidase (MPO) activities were assessed to monitor lipid peroxidation and neutrophil infiltration in liver tissue. Histologic liver damage was evaluated with hematoxylin-eosin stained slides. Liver tissue NF-κB and caspase-3 expression were studied immunohistopathologically to evaluate lipid peroxidation, liver damage, and hepatocyte apoptosis. RESULTS Forty-eight rats were evenly randomized into 6 groups of 8. MDA (P = 0.001), MPO (P = 0.001), NF-κB (P = 0.003), caspase-3 expression (P = 0.002), and liver injury scores (P = 0.002) increased significantly in the OJ group compared with the sham group. Compared with the OJ group, MDA (P = 0.030) and MPO levels (P = 0.001), and liver injury scores (P = 0.033) were decreased significantly in the OJ + sulfasalazine group. In the OJ + sulfasalazine + LPS and OJ + LPS + sulfasalazine groups, MDA (P = 0.008 and P = 0.023, respectively) and MPO (both, P = 0.001) were significantly decreased; however, liver NF-κB, caspase-3 expression, and liver injury scores were not significantly different compared with the OJ + LPS group. There was no significant difference between the OJ + LPS + sulfasalazine and OJ + sulfasalazine + LPS groups in regard to all end points when comparing the effects of sulfasalazine administered before or after sepsis. CONCLUSIONS Sulfasalazine was associated with decreased neutrophil accumulation and lipid peroxidation in these rats with OJ. Administration of sulfasalazine before or after LPS-induced sepsis was associated with a reduction in lipid peroxidation and neutrophil accumulation; however, it did not attenuate histologic liver damage. There was no difference between the findings when sulfasalazine was administered before or after sepsis in OJ.
Collapse
Affiliation(s)
- Musa Dirlik
- Department of General Surgery, Mersin University Medical School, Mersin, Turkey
| | - Aydin Karahan
- Department of General Surgery, Mersin University Medical School, Mersin, Turkey
| | - Hakan Canbaz
- Department of General Surgery, Mersin University Medical School, Mersin, Turkey
| | - Mehmet Caglikulekci
- Department of General Surgery, Mersin University Medical School, Mersin, Turkey
| | - Ayşe Polat
- Department of Pathology, Mersin University Medical School, Mersin, Turkey
| | - Lulufer Tamer
- Department of Biochemistry, Mersin University Medical School, Mersin, Turkey
| | - Suha Aydin
- Department of General Surgery, Mersin University Medical School, Mersin, Turkey
| |
Collapse
|
|
44
|
Wu Z, Kong X, Zhang T, Ye J, Fang Z, Yang X. Pseudoephedrine/ephedrine shows potent anti-inflammatory activity against TNF-α-mediated acute liver failure induced by lipopolysaccharide/D-galactosamine. Eur J Pharmacol 2013; 724:112-21. [PMID: 24365491 DOI: 10.1016/j.ejphar.2013.11.032] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2012] [Revised: 11/19/2013] [Accepted: 11/23/2013] [Indexed: 02/05/2023]
Abstract
The anti-inflammatory effects of pseudoephedrine/ephedrine were investigated using the experimental model of lipopolysaccharide (LPS)-induced acute liver failure in D-galactosamine (D-GalN)-sensitised male rats in order to elucidate effects other than sympathomimetic effects. Rats were intraperitoneally injected with D-GalN (400 mg/kg) and LPS (40 μg/kg) to induce acute liver failure. The treatment groups were then intraperitoneally administered pseudoephedrine/ephedrine at 0 h and 4 h after induction and the activation induced by treatment with pseudoephedrine and/or LPS on the primary Kupffer cells (KCs) was monitored. Compared with controls induced by GalN/LPS alone, pseudoephedrine dramatically reduced the infiltration of inflammatory cells and bile ductular hyperplasia and hepatic necrosis observed in liver sections. It inhibited both hepatocellular apoptosis and the expression of monocyte chemotactic protein-1. It lowered the production of tumour necrosis factor-α (TNF-α) in the beginning of acute liver failure induced by D-GalN/LPS. Correspondingly, levels of alanine aminotransferase (ALT), total bilirubin (TBIL) and malondialdehyde were attenuated. Ephedrine demonstrated all these identical protective effects as well. In addition, pseudoephedrine significantly suppressed the production of p-IκB-α, reducing the degradation of sequestered nuclear factor kappa B (NF-κB) in the cytoplasm, and inhibited the translocation of NF-κB/p65 to the nucleus, the transcription of TNF-α mRNA and the production of TNF-α in primary KCs. These results suggest that pseudoephedrine and ephedrine have a potent anti-inflammatory activity against D-GalN/LPS-induced acute liver failure in rats, and this comprehensive anti-inflammatory effect may result from the inhibition of TNF-α production.
Collapse
Affiliation(s)
- Zhongping Wu
- Teaching & Research Department of Clinical and Classic Medicine, College of Basic Medical Science, Shanghai University of Traditional Chinese Medicine, 1200 Cai lun Road, Shanghai 201203, China.
| | - Xiangliang Kong
- Teaching & Research Department of Clinical and Classic Medicine, College of Basic Medical Science, Shanghai University of Traditional Chinese Medicine, 1200 Cai lun Road, Shanghai 201203, China
| | - Tong Zhang
- Teaching & Research Department of Clinical and Classic Medicine, College of Basic Medical Science, Shanghai University of Traditional Chinese Medicine, 1200 Cai lun Road, Shanghai 201203, China
| | - Jin Ye
- Teaching & Research Department of Clinical and Classic Medicine, College of Basic Medical Science, Shanghai University of Traditional Chinese Medicine, 1200 Cai lun Road, Shanghai 201203, China
| | - Zhaoqin Fang
- Teaching & Research Department of Clinical and Classic Medicine, College of Basic Medical Science, Shanghai University of Traditional Chinese Medicine, 1200 Cai lun Road, Shanghai 201203, China
| | - Xuejun Yang
- Department of Nephrology, Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China.
| |
Collapse
|
|
45
|
Plumbagin, a Vitamin K3 Analogue, abrogates Lipopolysaccharide-Induced Oxidative Stress, Inflammation and Endotoxic Shock via NF-κB Suppression. Inflammation 2013; 37:542-54. [DOI: 10.1007/s10753-013-9768-y] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
|
|
46
|
A new sulfonic acid derivative, (Z)-4-methylundeca-1,9-diene-6-sulfonic acid, isolated from the cold water sea urchin inhibits inflammatory responses through JNK/p38 MAPK and NF-κB inactivation in RAW 264.7. Arch Pharm Res 2013; 37:983-91. [DOI: 10.1007/s12272-013-0269-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2013] [Accepted: 10/17/2013] [Indexed: 10/26/2022]
|
|
47
|
Huang YH, Yen JC, Lee JJ, Liao JF, Liaw WJ, Huang CJ. Suppressive effects of levobupivacaine on endotoxin-induced microglial activation. J Surg Res 2013; 184:989-96. [DOI: 10.1016/j.jss.2013.03.074] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2013] [Revised: 03/17/2013] [Accepted: 03/21/2013] [Indexed: 12/13/2022]
|
|
48
|
Khalaf H, Jass J, Olsson PE. The role of calcium, NF-κB and NFAT in the regulation of CXCL8 and IL-6 expression in Jurkat T-cells. INTERNATIONAL JOURNAL OF BIOCHEMISTRY AND MOLECULAR BIOLOGY 2013; 4:150-156. [PMID: 24049670 PMCID: PMC3776147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 08/16/2013] [Accepted: 09/06/2013] [Indexed: 06/02/2023]
Abstract
T-cells play an important role in host immunity against invading pathogens. Determining the underlying regulatory mechanisms will provide a better understanding of T-cell-derived immune responses. In this study, we have shown the differential regulation of IL-6 and CXCL8 by NF-κB and NFAT in Jurkat T-cells, in response to PMA, heat killed Escherichia coli and calcium. CXCL8 was closely associated with the activation pattern of NFAT, while IL-6 expression was associated with NF-κB. Furthermore, increasing the intracellular Ca(2+) concentration by calcium ionophore treatment of the cells resulted in NFAT induction without affecting the NF-κB activity. Interestingly, NF-κB activation by heat killed E. coli, as well as CXCL8 and IL-6 expression was significantly suppressed following addition of the calcium ionophore. This indicates that calcium plays an important role in regulating protein trafficking and T-cell signalling, and the subsequent inflammatory gene expression infers an involvement of NFAT in CXCL8 regulation.Understanding these regulatory patterns provide clarification of conditions that involve altered intracellular signalling leading to T-cell-derived cytokine expression.
Collapse
Affiliation(s)
- Hazem Khalaf
- The Life Science Centre, School of Science and Technology, Örebro University SE-701 82 Örebro, Sweden
| | | | | |
Collapse
|
|
49
|
An anti-inflammatory role of A20 zinc finger protein during trauma combined with endotoxin challenge. J Surg Res 2013; 185:717-25. [PMID: 24055365 DOI: 10.1016/j.jss.2013.06.031] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2013] [Revised: 05/27/2013] [Accepted: 06/13/2013] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To investigate the anti-inflammatory role of A20 zinc finger protein during trauma combined with bacterial endotoxin challenge and explore the molecular mechanism underlying this process. METHODS Traumatic bone impact injury was induced in the hind limbs of mice. One hour after injury, mice were challenged with purified gram-negative bacterial endotoxins, lipopolysaccharides (LPSs), by tail vein injection. Effects on A20 messenger RNA and protein expressions were assessed by reverse transcription-polymerase chain reaction and Western blotting, respectively. A20 recombinant adenoviruses, full-length (pAdA20 1-775) and N-terminal mutant (pAdA20 1-367), were constructed and used to infect RAW264.7 macrophage cells or mice. Responses in the tumor necrosis factor α (TNF-α)-nuclear factor κB (NF-κB) signaling pathway were evaluated by enzyme-linked immunosorbent assay (for TNF-α) and electrophoretic mobility shift assay (for NF-κB). RESULTS Trauma combined with LPS challenge and LPS challenge alone dramatically promoted A20 expression in mouse liver tissues. LPS challenge increased A20 messenger RNA levels appreciably in RAW264.7 cells within 1 h. Full-length A20 recombinant adenoviruses (pAdA20 1-775) suppressed NF-κB activity and TNF-α expression and protected against liver damage and animal death otherwise induced by trauma combined with LPS challenge. CONCLUSIONS A20 zinc finger protein plays an anti-inflammatory role and protects against liver injury associated with trauma combined with LPS challenge.
Collapse
|
|
50
|
Attenuation of Proinflammatory Responses by S-[6]-Gingerol via Inhibition of ROS/NF-Kappa B/COX2 Activation in HuH7 Cells. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 2013:146142. [PMID: 23843863 PMCID: PMC3697228 DOI: 10.1155/2013/146142] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/14/2013] [Revised: 05/17/2013] [Accepted: 05/24/2013] [Indexed: 02/06/2023]
Abstract
Introduction. Hepatic inflammation underlies the pathogenesis of chronic diseases such as insulin resistance and type 2 diabetes mellitus. S-[6]-Gingerol has been shown to have anti-inflammatory properties. Important inflammatory mediators of interleukins include nuclear factor κ B (NF κ B) and cyclooxygenase 2 (COX2). We now explore the mechanism of anti-inflammatory effects of S-[6]-gingerol in liver cells. Methods. HuH7 cells were stimulated with IL1β to establish an in vitro hepatic inflammatory model. Results. S-[6]-Gingerol attenuated IL1β-induced inflammation and oxidative stress in HuH7 cells, as evidenced by decreasing mRNA levels of inflammatory factor IL6, IL8, and SAA1, suppression of ROS generation, and increasing mRNA levels of DHCR24. In addition, S-[6]-gingerol reduced IL1β-induced COX2 upregulation as well as NF κ B activity. Similar to the protective effects of S-[6]-gingerol, both NS-398 (a selective COX2 inhibitor) and PDTC (a selective NF κ B inhibitor) suppressed mRNA levels of IL6, IL8, and SAA1. Importantly, PDTC attenuated IL1β-induced overexpression of COX2. Of particular note, the protective effect of S-[6]-gingerol against the IL1β-induced inflammatory response was similar to that of BHT, an ROS scavenger. Conclusions. The findings of this study demonstrate that S-[6]-gingerol protects HuH7 cells against IL1β-induced inflammatory insults through inhibition of the ROS/NF κ B/COX2 pathway.
Collapse
|