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Mechanisms of bradykinin‐induced expression of vascular cell adhesion molecule‐1 in human rheumatoid arthritis
Author(s) -
Wu PeiRung,
Yang ChuenMao
Publication year - 2008
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.22.1_supplement.1122.4
Subject(s) - p38 mitogen activated protein kinases , mapk/erk pathway , chemistry , cell adhesion molecule , nf κb , transfection , microbiology and biotechnology , cell adhesion , vcam 1 , tumor necrosis factor alpha , signal transduction , cancer research , cell , immunology , biology , icam 1 , biochemistry , gene
Increased expression of adhesion molecules by inflammatory mediators such as bradykinin (BK) plays a key role in inflammatory diseases during rheumatoid arthritis (RA). However, the mechanisms by which BK induced expression of vascular cell adhesion molecule‐1 (VCAM‐1) remained unknown in RA. Here, we reported that in human synovial fibroblasts, BK‐induced expression of VCAM‐1 protein, mRNA, and promoter gene activity was attenuated by the inhibitors of MEK1/2 (U0126), p38 MAPK (SB202190), JNK (SP600125), and NF‐κB (Bay11‐7082). Transfection with dominant‐negative plasmids of MEK, ERK1/2, p38, JNK, NIK, IKKα or IKKβ also abolished the VCAM‐1 expression. Accordingly, BK‐stimulated phosphorylation of p42/p44 MAPK, p38 MAPK, and JNK was also attenuated by pretreatment with U0126, SB202190, and SP600125, respectively. Moreover, BK‐induced NF‐κB activation was attenuated by pretreatment with U0126, SB202190, SP600125, or Bay11‐7082, determined by immunofluorescence staining. Furthermore, BK‐stimulated monocytes adhering on synovial fibroblasts via VCAM‐1 expression was decreased by pretreatment with U0126, SB202190, and SP600125. These results indicated that activation of ERK1/2, p38, JNK, and NF‐κB were involved in VCAM‐1 expression.