| Heme oxygenase-1 upregulation improves lipopolysaccharide-induced acute lung injury involving suppression of macrophage migration inhibitory factor. | |
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MedLine Citation:
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PMID: 20638132 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although studies have demonstrated that heme oxygenase-1 (HO-1) prevents leukocyte infiltration and organ damage following LPS challenge, the mechanisms involved in this protection are incompletely understood. Macrophage migration inhibitory factor (MIF) is thought to play a pivotal role in modulation of inflammatory and immune response through upregulation of TLR4 expression. Activation of TLR4 results in the production of proinflammatory mediators including MIF, which induce neutrophils recruitment and subsequent tissue insults. We hypothesized that HO-1 mediates its salutary effects in lipopolysaccharide (LPS)-induced inflammatory lung injury via downregulation of MIF through modulation of TLR4-induced proinflammatory mediator production. Compared with wild-type cells, MIF-knockdown macrophages in vitro are hyporesponsive to LPS stimulation, as shown by a profound reduction in TLR4 expression and TNF-alpha production. In the murine model of LPS-induced acute lung injury, administration of CoPP, a potent HO-1 inducer, leaded to a significant reduction in LPS-induced pulmonary edema, leucocytes influx, myeloperoxidase activity as well as histopathologic insults. Most strikingly, pretreatment with CoPP markedly decreased the expression of TLR4 and MIF in lung tissues in response to LPS challenge. These findings herein suggest that the cytoprotective functions of HO-1 in LPS-induced lung injury are associated with negative regulation of lung MIF and TLR4-induced inflammatory response. |
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Authors:
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Hui Yin; Xiangyong Li; Quan Gong; Xiaobao Jin; Hongbiao Gu; Baohong Yuan; Bobin Zhang; Fang Zheng; Feili Gong; Jiayong Zhu |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-16 |
Journal Detail:
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Title: Molecular immunology Volume: 47 ISSN: 1872-9142 ISO Abbreviation: Mol. Immunol. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-13 Completed Date: 2010-09-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7905289 Medline TA: Mol Immunol Country: England |
Other Details:
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Languages: eng Pagination: 2443-9 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acute Lung Injury
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chemically induced,
physiopathology* Animals Cell Line Cell Movement Gene Expression Regulation Heme Oxygenase-1 / biosynthesis, genetics, physiology* Inflammation Intramolecular Oxidoreductases / biosynthesis*, genetics Lipopolysaccharides / toxicity* Macrophage Migration-Inhibitory Factors / biosynthesis*, genetics Macrophages / metabolism* Male Membrane Proteins / biosynthesis, genetics, physiology* Mice Mice, Inbred BALB C Pyrazines / pharmacology Pyrroles / pharmacology RNA, Small Interfering / pharmacology Specific Pathogen-Free Organisms Toll-Like Receptor 4 / biosynthesis*, genetics Tumor Necrosis Factor-alpha / biosynthesis Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Lipopolysaccharides; 0/Macrophage Migration-Inhibitory Factors; 0/Membrane Proteins; 0/Pyrazines; 0/Pyrroles; 0/RNA, Small Interfering; 0/Tlr4 protein, mouse; 0/Toll-Like Receptor 4; 0/Tumor Necrosis Factor-alpha; 0/cyclohexyl-octahydro-pyrrolo(1,2-a)pyrazine; 0/lipopolysaccharide, Escherichia coli 0111 B4; EC 1.14.99.3/Heme Oxygenase-1; EC 1.14.99.3/Hmox1 protein, mouse; EC 5.3.-/Intramolecular Oxidoreductases; EC 5.3.2.1/Mif protein, mouse |
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