Activation of MEK/ERK pathways through NF-κB activation is involved in interleukin-1β-induced cyclooxygenease-2 expression in canine dermal fibroblasts
| Autor: | Hisashi Tsuchiya, Takanori Narita, Ken Okabayashi, Hiroshi Sugiya, Rei Nakano, Tadayoshi Konno |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
MAPK/ERK pathway MAP Kinase Signaling System medicine.medical_treatment Interleukin-1beta Immunology Biology Dinoprostone Gene Expression Regulation Enzymologic Proinflammatory cytokine Dogs medicine Animals RNA Messenger Prostaglandin E2 Wound Healing General Veterinary MEK inhibitor NF-kappa B Lipid signaling Fibroblasts Molecular biology IκBα Cyclooxygenase 2 Phosphorylation medicine.drug Prostaglandin E |
| Zdroj: | Veterinary Immunology and Immunopathology. 168:223-232 |
| ISSN: | 0165-2427 |
| DOI: | 10.1016/j.vetimm.2015.10.003 |
| Popis: | The proinflammatory cytokine interleukin-1β (IL-1β) induced cyclooxygenases-2 (COX-2) mRNA expression and lipid mediator prostaglandin E2 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-1β-induced prostaglandin E2 release and COX-2 mRNA expression. IL-1β enhanced ERK1/2 phosphorylation, which was attenuated by inhibitors of MEK and ERK. The NF-κB inhibitor BAY 11-7082 also suppressed IL-1β-induced prostaglandin E2 release and COX-2 mRNA expression. Treatment of fibroblasts with IL-1β led to the phosphorylation of p65 and degradation of IκBα occurred, indicating that IL-1β treatment activated NF-κB. MEK and ERK1/2 inhibitors had no effect on the phosphorylation of p65 subunit induced by IL-1β, whereas the NF-κB inhibitor completely blocked IL-1β-induced phosphorylation of ERK1/2. We also observed that IκBα-knockdown enhanced the phosphorylation of p65 and ERK1/2. These findings suggest that stimulation of MEK/ERK signaling pathway by NF-κB activation regulates IL-1β-induced COX-2 expression and subsequent prostaglandin E2 release in canine dermal fibroblasts. |
| Databáze: | OpenAIRE |
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