| Endogenous hydrogen sulfide regulates inflammatory response by activating the ERK pathway in polymicrobial sepsis. | |
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MedLine Citation:
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PMID: 18768890 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hydrogen sulfide (H(2)S) up-regulates inflammatory response in several inflammatory diseases. However, to date, little is known about the molecular mechanism by which H(2)S provokes the inflammatory response in sepsis. Thus, the aim of this study was to investigate the signaling pathway underlying the proinflammatory role of H(2)S in cecal ligation and puncture (CLP)-induced sepsis. Male Swiss mice were subjected to CLP and treated with dl-propargylglycine (PAG; 50 mg/kg i.p., an inhibitor of H(2)S formation), NaHS (10 mg/kg, i.p., an H(2)S donor), or saline. PAG was administered 1 h before CLP, whereas NaHS was given at the time of CLP. CLP-induced sepsis resulted in a time-dependent increase in the synthesis of endogenous H(2)S. Maximum phosphorylation of ERK1/2 and degradation of IkappaBalpha in lung and liver were observed 4 h after CLP. Inhibition of H(2)S formation by PAG significantly reduced the phosphorylation of ERK1/2 in lung and liver 4 h after CLP, coupled with decreased degradation of IkappaBalpha and activation of NF-kappaB. In contrast, injection of NaHS significantly enhanced the activation of ERK1/2 in lung and liver, therefore leading to a further rise in tissue NF-kappaB activity. As a result, pretreatment with PAG significantly reduced the production of cytokines and chemokines in sepsis, whereas exogenous H(2)S greatly increased it. In addition, pretreatment with PD98059, an inhibitor of ERK kinase (MEK-1), significantly prevented NaHS from aggravating systemic inflammation in sepsis. In conclusion, the present study shows for the first time that H(2)S may regulate systemic inflammatory response in sepsis via ERK pathway. |
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Authors:
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Huili Zhang; Shabbir M Moochhala; Madhav Bhatia |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 181 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2008 Sep |
Date Detail:
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Created Date: 2008-09-04 Completed Date: 2008-11-18 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 4320-31 Citation Subset: AIM; IM |
Affiliation:
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Department of Pharmacology, National University of Singapore, Singapore. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bacteremia / enzymology, metabolism, pathology Cecum / surgery Enzyme Activation / immunology Hydrogen Sulfide / blood, metabolism* Inflammation Mediators / blood, physiology* Ligation Male Mice Mitogen-Activated Protein Kinase 1 / metabolism*, physiology Mitogen-Activated Protein Kinase 3 / metabolism*, physiology NF-kappa B / metabolism, physiology Peritonitis / enzymology, metabolism, pathology Punctures Sepsis / enzymology*, immunology, metabolism, pathology* Signal Transduction / immunology* Up-Regulation / immunology |
| Chemical | |
Reg. No./Substance:
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0/Inflammation Mediators; 0/NF-kappa B; 7783-06-4/Hydrogen Sulfide; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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