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Interleukin‐17 and lipopolysaccharides synergistically induce cyclooxygenase‐2 expression in human intestinal myofibroblasts
Author(s) -
ZHANG ZHUOBIN,
ANDOH AKIRA,
INATOMI OSAMU,
BAMBA SHIGEKI,
TAKAYANAGI ATSUSHI,
SHIMIZU NOBUYOSHI,
FUJIYAMA YOSHIHIDE
Publication year - 2005
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2004.03748.x
Subject(s) - electrophoretic mobility shift assay , lipopolysaccharide , microbiology and biotechnology , interleukin , cyclooxygenase , gene expression , messenger rna , receptor , blot , inflammation , biology , medicine , immunology , cytokine , biochemistry , enzyme , gene
Background: Colonic subepithelial myofibroblasts (SEMF) play a role in the modulation of mucosal inflammatory responses via the secretion of various inflammatory mediators. In the present study the effects of interleukin (IL)‐17 and lipopolysaccharides (LPS) on cyclooxygenase (COX) expression in colonic SEMF were investigated. Methods: The expression of COX‐1 and ‐2 proteins and mRNAs were determined by western and northern blotting, respectively. Nuclear factor (NF)‐κB DNA binding activities were evaluated by electrophoretic gel mobility shift assays (EMSA). Results: The expression of COX‐2 protein and mRNA was rapidly induced by the addition of IL‐17 and LPS, whereas COX‐1 expression was not affected by these factors. The effects of IL‐17 and LPS were detected in a dose‐ and time‐dependent manner. Furthermore, IL‐17 and LPS synergistically induced COX‐2 mRNA and protein expression. The EMSA demonstrated that the addition of IL‐17 and LPS induced NF‐κB activation within 1.5 h after stimulation, and a blockade of NF‐κB activation by a recombinant adenovirus containing a stable form of IκBa markedly reduced the IL‐17‐ and LPS‐induced COX‐2 mRNA expression. In these cells, the expression of Toll‐like receptor (TLR)‐4, which is a cellular receptor for LPS, was detected. Conclusion: Interleukin‐17 and LPS play an important role in the induction of COX‐2 in SEMF. These findings suggest that COX‐2 expression and prostaglandin synthesis might be regulated by both T‐cell‐derived factor (IL‐17) and bacterial products (LPS) in the inflamed mucosa.