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TNF‐α‐induced VCAM‐1 expression via MAPKs and NF‐κB in human fibroblast‐like synoviocytes
Author(s) -
Fang YuYen,
Yang ChuenMao
Publication year - 2006
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.20.4.a225
Subject(s) - p38 mitogen activated protein kinases , nf κb , mapk/erk pathway , kinase , vcam 1 , transfection , microbiology and biotechnology , chemistry , tumor necrosis factor alpha , iκb kinase , iκbα , cell adhesion molecule , phosphorylation , signal transduction , biology , icam 1 , biochemistry , immunology , gene
TNF‐α has been shown to induce the expression of adhesion molecules in rheumatoid arthritis and contribute to inflammatory responses. Here, the roles of mitogen‐activated protein kinases (MAPKs) and NF‐κB in TNF‐α‐induced expression of vascular cell adhesion molecule (VCAM)‐1 were investigated in human fibroblast‐like synoviocytes (FLS). TNF‐α‐enhanced expression of VCAM‐1 and phosphorylation of p42/p44 MAPK, p38, and JNK were attenuated by inhibitors of MEK1/2 (U0126), p38 (SB202190), JNK (SP600125), and transfection with dominant negative mutants of MEK1/2, ERK1, p38, and JNK. Furthermore, TNF‐α‐induced VCAM‐1 expression was blocked by a selective NF‐κB inhibitor helenalin and transfection with dominant negative plasmids of NF‐κB‐inducing kinase (NIK), IKK‐α and IKK‐β. Consistently, TNF‐α‐stimulated translocation of NF‐κB into the nucleus and degradation of IκB‐α was revealed by Western blotting and immnofluorescence staining, which was blocked by helenalin, but not by U0126, SB202190, or SP600125. Taken together, these results suggest that in FLS, activation of p42/p44 MAPK, p38, JNK and NF‐κB pathways is essential for TNF‐α‐induced VCAM‐1 gene expression via transcription and translation processes.