RRC ID 12203
Author Miyazawa K, Mori A, Miyata H, Akahane M, Ajisawa Y, Okudaira H.
Title Regulation of interleukin-1beta-induced interleukin-6 gene expression in human fibroblast-like synoviocytes by p38 mitogen-activated protein kinase.
Journal J Biol Chem
Abstract Involvement of p38 mitogen-activated protein (MAP) kinase in interleukin (IL)-6 gene expression of human fibroblast-like synoviocytes (FLSs) was assessed. p38 MAP kinase was constitutively expressed in human FLSs and activated in response to IL-1beta. A pyridinylimidazole compound, SB203580, inhibited p38 MAP kinase activity in vivo, since the activity of MAPKAP kinase-2 (a substrate of p38 MAP kinase) in IL-1beta-stimulated FLSs was totally suppressed by it. SB203580 concentration-dependently inhibited protein production and gene expression of IL-6 by human FLSs. The effect of SB203580 was dependent on de novo protein synthesis. SB203580 significantly reduced the stability of IL-6 mRNA without affecting the rate of IL-6 gene transcription. Here, we provide evidence that p38 MAP kinase is activated in response to IL-1beta in human FLSs and is involved in IL-6 synthesis by stabilizing IL-6 mRNA.
Volume 273(38)
Pages 24832-8
Published 1998-9-18
DOI 10.1074/jbc.273.38.24832
PMID 9733787
MeSH Anti-Inflammatory Agents / pharmacology Arthritis, Rheumatoid / genetics Arthritis, Rheumatoid / immunology Arthritis, Rheumatoid / pathology Calcium-Calmodulin-Dependent Protein Kinases / metabolism* Cell Nucleus / metabolism Cells, Cultured Cycloheximide / pharmacology Dactinomycin / pharmacology Dose-Response Relationship, Drug Fibroblasts / drug effects Fibroblasts / immunology Gene Expression Regulation / drug effects Gene Expression Regulation / immunology* Humans Imidazoles / pharmacology Interleukin-1 / pharmacology* Interleukin-1 / physiology Interleukin-6 / biosynthesis Interleukin-6 / genetics* Intracellular Signaling Peptides and Proteins Kinetics Mitogen-Activated Protein Kinases* NF-kappa B / metabolism Osteoarthritis / genetics Osteoarthritis / immunology Osteoarthritis / pathology Protein-Serine-Threonine Kinases / metabolism Pyridines / pharmacology Recombinant Proteins / pharmacology Synovial Membrane / drug effects Synovial Membrane / immunology* Synovial Membrane / pathology p38 Mitogen-Activated Protein Kinases
IF 4.238
Times Cited 195
DNA material pGEMhIL-6 GT Human IL-6 genomic clone (RDB01211)