Interleukin-1beta increases gap junctional communication among synovial fibroblasts via the extracellular-signal-regulated kinase pathway.
Interleukin-1beta increases gap junctional communication among synovial fibroblasts via the extracellular-signal-regulated kinase pathway.
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DOI：
10.1042/bc20090056
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发表时间：
2009-10-12
影响因子：
2.7
通讯作者：
Stains JP
中科院分区：
文献类型：
--
作者：
Niger C;Howell FD;Stains JP
The gap junction protein, connexin43, has been implicated in the etiology of osteoarthritis. Work from others has revealed that the size and number of gap junctions increases in synovial biopsies from patients with osteoarthritis. Further, pharmacologic inhibition of connexin43 function has been shown to reduce interleukin-1β induced metalloproteinase production by synovial fibroblasts in vitro. In this study, we examine the link between interleukin-1β and connexin43 function. We demonstrate that treatment of a rabbit synovial fibroblast cell line with interleukin-1β markedly increases connexin43 protein in a dose- and time-dependent manner. The impact on connexin43 protein levels appears to occur post-transcriptionally as mRNA levels are unaffected by interleukin-1β administration. Additionally, we show by fluorescence microscopy that interleukin-1β alters the cellular distribution of connexin43 to cell-cell junctions and is concomitant to a striking increase in gap junction communication. Further, we demonstrate that the increase in connexin43 protein and the associated change in protein localization and gap junction communication following interleukin-1β treatment are dependent upon activation of the extracellular signal regulated kinase signaling cascade. These data show that interleukin-1β acts through the extracellular signal regulated kinase signaling cascade to alter the expression and function of connexin43 in synovial fibroblasts.
