RRC ID |
12203
|
著者 |
Miyazawa K, Mori A, Miyata H, Akahane M, Ajisawa Y, Okudaira H.
|
タイトル |
Regulation of interleukin-1beta-induced interleukin-6 gene expression in human fibroblast-like synoviocytes by p38 mitogen-activated protein kinase.
|
ジャーナル |
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.
|
巻・号 |
273(38)
|
ページ |
24832-8
|
公開日 |
1998-9-18
|
DOI |
10.1074/jbc.273.38.24832
|
PII |
S0021-9258(19)60156-0
|
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
|
引用数 |
195
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
遺伝子材料 |
pGEMhIL-6 GT Human IL-6 genomic clone (RDB01211) |