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TNF‐α‐induced cyclooxygenase‐2 expression in human synoviocytes
Author(s) -
Chen ChunHua,
Yang ChuenMao
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.571.5
Subject(s) - p38 mitogen activated protein kinases , mapk/erk pathway , tumor necrosis factor alpha , phosphorylation , nf κb , pathogenesis , kinase , signal transduction , cyclooxygenase , iκbα , blot , arthritis , transfection , chemistry , microbiology and biotechnology , cancer research , biology , immunology , gene , enzyme , biochemistry
COX‐2 is implicated in the pathogenesis of rheumatoid arthritis (RA) and has previously been shown to be induced by TNF‐α is implicated in the pathogenesis of rheumatoid arthritis (RA) and has previously been shown to be induced by TNF‐α. However, the molecular mechanisms underlying TNF‐α‐induced cyclooxygenase‐2 (COX‐2) expression in human synoviocytes (HS) which contributes to inflammatory responses in RA were largely unknown. Here, Western blotting and RT‐PCR analyses showed that TNF‐α induced COX‐2 protein and mRNA expression as well as phosphorylation of p42/p44 MAPK, p38 MAPK, and JNK which was attenuated by the inhibitors of MEK1/2 (U0126), p38 MAPK (SB202190), and JNK (SP600125), and transfection with siRNA of ERK1, p38, and JNK2, respectively. Furthermore, TNF‐α‐induced COX‐2 expression was inhibited by a selective NF‐¿B inhibitor (Bay11‐7082) and consistent with that TNF‐α stimulated both I¿B‐α degradation and NF‐¿B translocation into nucleus in these cells. NF‐¿B translocation was blocked by Bay11‐7082, but not by U0126, SB202190, and SP600125. Taken together, these results suggested that in HS, TNF‐α‐induced COX‐2 expression was independently mediated through phosphorylation of MAPKs and NF‐¿B pathways.