title: Activation of MEK/ERK pathways through NF-κB activation is involved in interleukin-1β-induced cyclooxygenease-2 expression in canine dermal fibroblasts.
abstract: 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.
authors.affiliation: Laboratory of Veterinary Biochemistry, Nihon University College of Bioresource Sciences, Fujisawa, Kanagawa 252-0880, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Tsuchiya
authors.affiliation: Laboratory of Veterinary Biochemistry, Nihon University College of Bioresource Sciences, Fujisawa, Kanagawa 252-0880, Japan.
authors.forename: Rei
authors.initials: R
authors.lastname: Nakano
authors.affiliation: Laboratory of Veterinary Biochemistry, Nihon University College of Bioresource Sciences, Fujisawa, Kanagawa 252-0880, Japan.
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Konno
authors.affiliation: Laboratory of Veterinary Biochemistry, Nihon University College of Bioresource Sciences, Fujisawa, Kanagawa 252-0880, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Okabayashi
authors.affiliation: Laboratory of Veterinary Biochemistry, Nihon University College of Bioresource Sciences, Fujisawa, Kanagawa 252-0880, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Narita
authors.affiliation: Laboratory of Veterinary Biochemistry, Nihon University College of Bioresource Sciences, Fujisawa, Kanagawa 252-0880, Japan. Electronic address: sugiya.hiroshi@nihon-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiya
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology*; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; D015232:Dinoprostone
keywords: COX-2; Canine dermal fibroblasts; ERK1/2; IL-1β; NF-κB; Prostaglandin E(2)