論文 - 詳細
| RRC ID | 38809 |
|---|---|
| 著者 | Joto N, Akimoto T, Someya K, Tohgo A. |
| タイトル | Production of tumor necrosis factor induced by synthetic low-toxicity lipid A analog, DT-5461a, is mediated by LPS receptor sites and tyrosine kinase-MAP kinase signaling pathway in murine macrophages. |
| ジャーナル | Cell Immunol |
| Abstract |
The synthetic low-toxicity lipid A analog DT-5461a induces endogenous TNF production in mice. The activity of TNF so induced is probably the main contributor to the antitumor effect of this compound. In the present study, we investigated the mechanism by which DT-5461a induces TNF production in murine macrophage RAW 264 cells. DT-5461a mimicked the ability of LPS to induce TNF production in a dose-dependent manner. DT-5461a at higher concentrations inhibited specific binding of [3H]LPS to the cells and reduced LPS-induced TNF production to the level induced by DT-5461a alone. In addition, DT-5461a, as well as LPS, induced tyrosine phosphorylation of MAP kinases, the early signal transduction pathway of this production. Herbimycin A, an inhibitor of tyrosine kinase, inhibited the LPS- and DT-5461a-induced tyrosine phosphorylation, expression of TNF mRNA, and subsequent TNF secretion. These results suggest that DT-5461a and LPS induce TNF production in murine macrophages through the common receptor sites and the similar early signaling pathway. |
| 巻・号 | 160(1) |
| ページ | 1-7 |
| 公開日 | 1995-1-1 |
| DOI | 10.1016/0008-8749(95)80002-z |
| PII | 0008-8749(95)80002-Z |
| PMID | 7531115 |
| MeSH | Animals Benzoquinones Binding, Competitive Blotting, Western Cell Line, Transformed Disaccharides / pharmacology* Lactams, Macrocyclic Lipid A / analogs & derivatives* Lipid A / pharmacology Lipopolysaccharide Receptors Lipopolysaccharides / metabolism Lipopolysaccharides / pharmacology Macrophages / immunology* Mice Protein Kinases / physiology* Protein-Tyrosine Kinases / physiology Quinones / pharmacology RNA, Messenger / biosynthesis RNA, Messenger / drug effects Receptors, Immunologic / physiology* Rifabutin / analogs & derivatives Signal Transduction / immunology* Tumor Necrosis Factor-alpha / biosynthesis* |
| IF | 4.078 |
| 引用数 | 9 |
| WOS 分野 | IMMUNOLOGY CELL BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |