期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 224, 期 2, 页码 516-526出版社
WILEY
DOI: 10.1002/jcp.22153
关键词
-
资金
- National Science Council, Taiwan [NSC95-2320-182-047-MY3]
- Chang Gung Medical Research Foundation [CMRPG350643, CMRPG350653, CMRPD180061]
Interleukin-1 beta (IL-1 beta) has been shown to induce the expression of adhesion molecules on various cell types and contributes to inflammatory responses. However, the molecular mechanisms by which IL-1 beta induced intercellular adhesion molecule (ICAM)-1 expression remain unclear in human rheumatoid arthritis synovial fibroblasts (RASFs). Here, we demonstrated that IL-1 beta induces ICAM-1 gene expression via the de novo protein synthesis through transcription and translation, which is attenuated by pretreatment with actinomycin D and cycloheximide, respectively. IL-1 beta-induced ICAM-1 expression, extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (INK) phosphorylation, AP-1 activation, and nuclear factor-kappa B (NF-kappa B) p65 translocation were attenuated by the inhibitors of MEK1/2 (U0126), JNK (SP600125), AP-1 (tanshinoneIIA), and NF-kappa B (helenalin) or transfection with respective short hairpin RNA plasmids. Moreover, IL-1 beta-stimulated NF-kappa B p65 translocation was blocked by helenalin, but not by U0126 or SP600125, revealing that MAPKs and NF-kappa B pathways were independent on these responses. IL-1 beta-stimulated AP-1 activation was blocked by U0126 or SP600125, revealing that ERK and JNK linked to AP-1 on these responses. IL-1 beta-stimulated ICAM-1 gene expression was attenuated by pretreatment with U0126, SP600125, tanshinone IIA, or helenalin, revealed by ICAM-1 promoter assay and real-time RT-PCR analysis. Finally, up-regulation of ICAM-1 enhanced the adhesion of leukocytes to RASFs exposed to IL-1 beta. These results suggest that in human RASFs, activation of ERK, JNK, AP-1, and NE-kappa B are essential for IL-1 beta-induced ICAM-1 expression and leukocyte adhesion. J. Cell. Physiol. 224: 516-526, 2010. (C) 2010 Wiley-Liss, Inc.
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