Document Detail


TLR4 monoclonal antibody blockade suppresses dextran-sulfate-sodium-induced colitis in mice.
MedLine Citation:
PMID:  19929926     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND AIM: Ulcerative colitis (UC) refers to a kind of inflammatory bowel disease, of which the accurate pathogenesis is not yet well understood. Recently, the toll-like receptor 4 (TLR4) and the TLR4 signaling pathway have been proved as playing an important role in the pathogenesis of UC. The objective of this study was to evaluate the effect of TLR4 monoclonal antibody on dextran-sulfate-sodium-induced colitis in a mouse model. METHODS: We evaluated the effects of the TLR4 monoclonal antibody (TLR4mAb) on the development of dextran-sulfate-sodium-(DSS)-induced colitis. Tissue samples were evaluated by the disease activity index and histopathological score. Meanwhile, the mucosal mRNA expression of cytokines, tumor necrosis factor-alpha, interferon-gamma and interleukin-1beta were analyzed by semiquantitative reverse transcription polymerase chain reaction. The mucosal protein P38-MAPK, c-jun and c-fos expressions of the TLR4-P38MAPK pathway were analyzed using Western blot. RESULTS: After the treatment with TLR4mAb against DSS-induced colitis, the bodyweight was significantly increased and both disease activity index and histopathological score were decreased significantly. Furthermore, the mucosal expression of messenger RNA of tumor necrosis factor-alpha, interferon-gamma and interleukin-1beta were observed to be 8-15-fold more than the baseline, whereas the mucosal expressions of P38MAPK and c-jun were found to be decreased. CONCLUSION: Blocking TLR4 by TLR4mAb can prevent the development of DSS-induced colitis through the TLR4-P38MAPK-c-jun pathway.
Authors:
Yi Liu; Zhijun Zhang; Lei Wang; Juan Li; Le Dong; Wenjie Yue; Jian Chen; Xu Sun; Liang Zhong; Dayu Sun
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-19
Journal Detail:
Title:  Journal of gastroenterology and hepatology     Volume:  25     ISSN:  1440-1746     ISO Abbreviation:  J. Gastroenterol. Hepatol.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-02-08     Completed Date:  2010-05-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8607909     Medline TA:  J Gastroenterol Hepatol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  209-14     Citation Subset:  IM    
Affiliation:
Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai, China. liuyi0205@sina.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / pharmacology*
Blotting, Western
Body Weight / drug effects
Colitis / chemically induced,  immunology,  pathology,  prevention & control*
Colon / drug effects*,  immunology,  pathology
Dextran Sulfate
Disease Models, Animal
Interferon-gamma / genetics
Interleukin-1beta / genetics
Male
Mice
Mice, Inbred BALB C
Proto-Oncogene Proteins c-fos / metabolism
Proto-Oncogene Proteins c-jun / metabolism
RNA, Messenger / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Severity of Illness Index
Signal Transduction / drug effects
Toll-Like Receptor 4 / antagonists & inhibitors*,  immunology
Tumor Necrosis Factor-alpha / genetics
p38 Mitogen-Activated Protein Kinases / metabolism
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Interleukin-1beta; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/RNA, Messenger; 0/Tlr4 protein, mouse; 0/Toll-Like Receptor 4; 0/Tumor Necrosis Factor-alpha; 82115-62-6/Interferon-gamma; 9042-14-2/Dextran Sulfate; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases

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