Interleukin-1β induces ICAM-1 expression enhancing leukocyte adhesion in human rheumatoid arthritis synovial fibroblasts: Involvement of ERK, JNK, AP-1, and NF-κB

Chuen Mao Yang*, Shue Fen Luo, Hsi Lung Hsieh, Pei Ling Chi, Chih Chung Lin, Chi Chuan Wu, Li Der Hsiao

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

79 Scopus citations

Abstract

Interleukin-1β (IL-1β) 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-1β induced intercellular adhesion molecule (ICAM)-1 expression remain unclear in human rheumatoid arthritis synovial fibroblasts (RASFs). Here, we demonstrated that IL-1β 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-1β-induced ICAM-1 expression, extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK) phosphorylation, AP-1 activation, and nuclear factor-κB (NF-κB) p65 translocation were attenuated by the inhibitors of MEK1/2 (U0126), JNK (SP600125), AP-1 (tanshinone IIA), and NF-κB (helenalin) or transfection with respective short hairpin RNA plasmids. Moreover, IL-1β-stimulated NF-κB p65 translocation was blocked by helenalin, but not by U0126 or SP600125, revealing that MAPKs and NF-κB pathways were independent on these responses. IL-1β-stimulated AP-1 activation was blocked by U0126 or SP600125, revealing that ERK and JNK linked to AP-1 on these responses. IL-1β-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-1β. These results suggest that in human RASFs, activation of ERK, JNK, AP-1, and NF-κB are essential for IL-1β-induced ICAM-1 expression and leukocyte adhesion.

Original languageEnglish
Pages (from-to)516-526
Number of pages11
JournalJournal of Cellular Physiology
Volume224
Issue number2
DOIs
StatePublished - 08 2010
Externally publishedYes

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