論文 - 詳細
| RRC ID | 65988 |
|---|---|
| 著者 | Rossa C, Ehmann K, Liu M, Patil C, Kirkwood KL. |
| タイトル | MKK3/6-p38 MAPK signaling is required for IL-1beta and TNF-alpha-induced RANKL expression in bone marrow stromal cells. |
| ジャーナル | J Interferon Cytokine Res |
| Abstract |
Coupled bone turnover is directed by the expression of receptor-activated NF-kappaB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). Proinflammatory cytokines, such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) induce RANKL expression in bone marrow stromal cells. Here, we report that IL-1beta and TNF-alpha-induced RANKL requires p38 mitogen-activating protein kinase (MAPK) pathway activation for maximal expression. Real-time PCR was used to assess the p38 contribution toward IL-1beta and TNF-alpha-induced RANKL mRNA expression. Steady-state RANKL RNA levels were increased approximately 17-fold by IL-1beta treatment and subsequently reduced approximately 70%-90% when p38 MAPK was inhibited with SB203580. RANKL mRNA stability data indicated that p38 MAPK did not alter the rate of mRNA decay in IL-1beta-induced cells. Using a RANKL-luciferase cell line receptor containing a 120-kB segment of the 5' flanking region of the RANKL gene, reporter expression was stimulated 4-5-fold by IL-1beta or TNF-alpha treatment. IL-1beta-induced RANKL reporter expression was completely blocked with specific p38 inhibitors as well as dominant negative mutant constructs of MAPK kinase-3 and -6. In addition, blocking p38 signaling in bone marrow stromal cells partially inhibited IL-1beta and TNF-alpha-induced osteoclastogenesis in vitro. Results from these studies indicate that p38 MAPK is a major signaling pathway involved in IL-1beta and TNF-alpha-induced RANKL expression in bone marrow stromal cells. |
| 巻・号 | 26(10) |
| ページ | 719-29 |
| 公開日 | 2006-10-1 |
| DOI | 10.1089/jir.2006.26.719 |
| PMID | 17032166 |
| MeSH | Animals Bone Marrow Cells / drug effects Bone Marrow Cells / enzymology Bone Marrow Cells / metabolism* Carrier Proteins / biosynthesis* Carrier Proteins / genetics Cell Differentiation Cell Line Cytokines / pharmacology* Genes, Reporter Imidazoles / pharmacology Interleukin-1 / antagonists & inhibitors Interleukin-1 / pharmacology MAP Kinase Kinase 3 / antagonists & inhibitors MAP Kinase Kinase 3 / genetics MAP Kinase Kinase 3 / metabolism MAP Kinase Kinase 6 / antagonists & inhibitors MAP Kinase Kinase 6 / genetics MAP Kinase Kinase 6 / metabolism MAP Kinase Signaling System / drug effects Membrane Glycoproteins / biosynthesis* Membrane Glycoproteins / genetics Mice Mitogen-Activated Protein Kinase Kinases / metabolism* Mutation Osteoclasts / cytology Protein Kinase Inhibitors / pharmacology Pyridines / pharmacology RANK Ligand RNA, Messenger / metabolism Receptor Activator of Nuclear Factor-kappa B Stromal Cells / drug effects Stromal Cells / enzymology Stromal Cells / metabolism Transcriptional Activation Tumor Necrosis Factor-alpha / antagonists & inhibitors Tumor Necrosis Factor-alpha / pharmacology p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors p38 Mitogen-Activated Protein Kinases / metabolism* |
| IF | 2.032 |
| リソース情報 | |
| ヒト・動物細胞 | ST2(RCB0224) |