title: JNK activation is essential for activation of MEK/ERK signaling in IL-1β-induced COX-2 expression in synovial fibroblasts.
abstract: The proinflammatory cytokine interleukin 1β (IL-1β) induces prostaglandin E2(PGE2) production via upregulation of cyclooxygenase-2 (COX-2) expression in synovial fibroblasts. This effect of IL-1β is involved in osteoarthritis. We investigated MAPK signaling pathways in IL-1β-induced COX-2 expression in feline synovial fibroblasts. In the presence of MAPK inhibitors, IL-1β-induced COX-2 expression and PGE2release were both attenuated. IL-1β induced the phosphorylation of p38, JNK, MEK, and ERK1/2. A JNK inhibitor prevented not only JNK phosphorylation but also MEK and ERK1/2 phosphorylation in IL-1β-stimulated cells, but MEK and ERK1/2 inhibitors had no effect on JNK phosphorylation. A p38 inhibitor prevented p38 phosphorylation, but had no effect on MEK, ERK1/2, and JNK phosphorylation. MEK, ERK1/2, and JNK inhibitors had no effect on p38 phosphorylation. We also observed that in IL-1β-treated cells, phosphorylated MEK, ERK1/2, and JNK were co-precipitated with anti-phospho-MEK, ERK1/2, and JNK antibodies. The silencing of JNK1 in siRNA-transfected fibroblasts prevented IL-1β to induce phosphorylation of MEK and ERK1/2 and COX-2 mRNA expression. These observations suggest that JNK1 phosphorylation is necessary for the activation of the MEK/ERK1/2 pathway and the subsequent COX-2 expression for PGE2release, and p38 independently contributes to the IL-1β effect in synovial fibroblasts.
authors.affiliation: Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Kitanaka
authors.affiliation: Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa, Japan.
authors.forename: Rei
authors.initials: R
authors.lastname: Nakano
authors.affiliation: Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa, Japan.
authors.forename: Nanako
authors.initials: N
authors.lastname: Kitanaka
authors.affiliation: Kimura Animal Hospital, 50 Babashitacho, Shinjuku, Tokyo, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Okabayashi
authors.affiliation: Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Narita
authors.affiliation: Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiya
mesh_terms: D000818:Animals; D002415:Cats; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005347:Fibroblasts / Q000502:physiology*; D053583:Interleukin-1beta / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D053583:Interleukin-1beta; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D048055:Mitogen-Activated Protein Kinase 8; D020930:MAP Kinase Kinase Kinases; D015232:Dinoprostone