Document Detail

Heme oxygenase-1 upregulation improves lipopolysaccharide-induced acute lung injury involving suppression of macrophage migration inhibitory factor.
MedLine Citation:
PMID:  20638132     Owner:  NLM     Status:  MEDLINE    
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.
Hui Yin; Xiangyong Li; Quan Gong; Xiaobao Jin; Hongbiao Gu; Baohong Yuan; Bobin Zhang; Fang Zheng; Feili Gong; Jiayong Zhu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-16
Journal Detail:
Title:  Molecular immunology     Volume:  47     ISSN:  1872-9142     ISO Abbreviation:  Mol. Immunol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-13     Completed Date:  2010-09-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7905289     Medline TA:  Mol Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  2443-9     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ltd. All rights reserved.
Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, China.
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MeSH Terms
Acute Lung Injury / chemically induced,  physiopathology*
Cell Line
Cell Movement
Gene Expression Regulation
Heme Oxygenase-1 / biosynthesis,  genetics,  physiology*
Intramolecular Oxidoreductases / biosynthesis*,  genetics
Lipopolysaccharides / toxicity*
Macrophage Migration-Inhibitory Factors / biosynthesis*,  genetics
Macrophages / metabolism*
Membrane Proteins / biosynthesis,  genetics,  physiology*
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
Reg. No./Substance:
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 Oxygenase-1; EC protein, mouse; EC 5.3.-/Intramolecular Oxidoreductases; EC protein, mouse

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