Interleukin‐1 β increases gap junctional communication among synovial fibroblasts via the extracellular‐signal‐regulated kinase pathway
Open Access
- 3 January 2010
- journal article
- Published by Wiley in Biology of the Cell
- Vol. 102 (1), 37-49
- https://doi.org/10.1042/bc20090056
Abstract
Background information . The gap junction protein, Cx43 (connexin 43), has been implicated in the aetiology of osteoarthritis. Studies have revealed that the size and number of gap junctions increase in synovial biopsies from patients with osteoarthritis. Furthermore, pharmacological inhibition of Cx43 function has been shown to reduce IL‐1β (interleukin‐1β)‐induced metalloproteinase production by synovial fibroblasts in vitro . Results . In the present study, we examined the link between IL‐1β and Cx43 function. We demonstrated that treatment of a rabbit synovial fibroblast cell line with IL‐1β markedly increased the level of the Cx43 protein in a concentration‐ and time‐dependent manner. The impact on Cx43 protein levels appeared to occur post‐transcriptionally, as mRNA levels are unaffected by IL‐1β administration. Additionally, we showed by fluorescence microscopy that IL‐1β alters the cellular distribution of Cx43 to cell–cell junctions and is concomitant with a striking increase in gap junction communication. Furthermore, we demonstrated that the increase in Cx43 protein, and the associated change in protein localization and gap junction communication following IL‐1β treatment, are dependent upon activation of the ERK (extracellular‐signal‐regulated kinase) signalling cascade. Conclusion . These data show that IL‐1β acts through the ERK signalling cascade to alter the expression and function of Cx43 in synovial fibroblasts.Keywords
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