Activation of MEK/ERK pathways through NF-kappa B activation is involved in interleukin-1 beta-induced cyclooxygenease-2 expression in canine dermal fibroblasts

作者：Tsuchiya Hisashi; Nakano Rei; Konno Tadayoshi; Okabayashi Ken; Narita Takanori; Sugiya Hiroshi^*

来源：Veterinary Immunology and Immunopathology, 2015, 168(3-4): 223-232.

DOI：10.1016/j.vetimm.2015.10.003

• NF-kappa B
• ERK1/2
• IL-1 beta
• COX-2
• Prostaglandin E-2
• Canine dermal fibroblasts

The proinflammatory cytokine interleukin-1 beta (IL-1 beta) induced cyclooxygenases-2 (COX-2) mRNA expression and lipid mediator prostaglandin E-2 release and in a time- and dose-dependent manner in canine dermal fibroblasts. The MEK inhibitor U0126 and the ERK inhibitor FR180204 clearly inhibited IL-1 beta-induced prostaglandin E-2 release and COX-2 mRNA expression. IL-1 beta enhanced ERK1/2 phosphorylation, which was attenuated by inhibitors of MEK and ERK. The NF-kappa B inhibitor BAY 11-7082 also suppressed IL-1 beta-induced prostaglandin E-2 release and COX-2 mRNA expression. Treatment of fibroblasts with IL-1 beta led to the phosphorylation of p65 and degradation of I kappa B alpha occurred, indicating that IL-1 beta treatment activated NF-kappa B. MEK and ERK1/2 inhibitors had no effect on the phosphorylation of p65 subunit induced by IL-1 beta, whereas the NF-kappa B inhibitor completely blocked IL-1 beta-induced phosphorylation of ERK1/2. We also observed that I kappa B alpha-knockdown enhanced the phosphorylation of p65 and ERK1/2. These findings suggest that stimulation of MEK/ERK signaling pathway by NF-kappa B activation regulates IL-1 beta-induced COX-2 expression and subsequent prostaglandin E-2 release in canine dermal fibroblasts.

• 出版日期2015-12-15