Interleukin-1β promotes interleulin-6 expression via ERK1/2 signaling pathway in canine dermal fibroblasts

Interleukin-6 (IL-6) is a pleiotropic cytokine involved in the regulation of the immune response and inflammation. In this study, we investigated effect of the proinflammatory cytokine interleukin-1 beta (IL-1 beta) on IL-6 expression in canine dermal fibroblasts. IL-1 beta induced IL-6 mRNA expression and protein release in a time-and dose-dependent manner. When cells were treated with inhibitors of mitogen-activated protein kinases (MAPKs), the extracellular signal-regulated kinase (ERK) inhibitor FR180240 inhibited IL-1 beta-induced IL-6 mRNA expression, but not SP600125 or SKF86002, which are c-Jun N-terminal kinase (JNK) and p38 MAPK inhibitors, respectively. In cells treated with U0126, an inhibitor of MAPK/ERK kinase (MEK), which activates ERK, IL-1 beta-induced IL-6 mRNA expression was also inhibited. IL-1 beta stimulated ERK1/2 phosphorylation. In cells transfected with ERK1 and ERK2 isoform siRNAs, IL-1 beta-induced IL-6 mRNA expression was reduced. These observations suggest that IL-1 beta induces IL-6 expression via ERK1/2 signaling pathway in canine dermal fibroblasts.