論文 - 詳細
| RRC ID | 39812 |
|---|---|
| 著者 | Lakics V, Medvedev AE, Okada S, Vogel SN. |
| タイトル | Inhibition of LPS-induced cytokines by Bcl-xL in a murine macrophage cell line. |
| ジャーナル | J Immunol |
| Abstract |
The antiapoptotic molecule Bcl-xL has been implicated in the differentiation and survival of activated macrophages in inflammatory conditions. In this report, the role of Bcl-xL in LPS-induced cytokine gene expression and secretion was studied. Bcl-xL-transfected RAW 264 macrophages were protected from gliotoxin-induced apoptosis, indicating the presence of functional Bcl-xL. Overexpression of Bcl-xL in this macrophage cell line was also associated with a marked inhibition of LPS-induced TNF-alpha, JE/monocyte chemoattractant protein 1, and macrophage inflammatory protein 2 secretion. Inhibition of LPS-induced cytokine secretion was paralleled by a decrease in levels of steady-state mRNA for the above cytokines and for IL-1beta. Decreased production of TNF-alpha in Bcl-xL transfectants was not due to increased mRNA degradation, as the mRNA half-lives were the same in Bcl-xL transfectants and control macrophages. Although the composition of NF-kappaB complexes detected by EMSA and supershift analysis in nuclear lysates derived from Bcl-xL transfectants and control cells was indistinguishable, LPS-induced inhibitory kappaBalpha degradation, as well as NF-kappaB binding and AP-1 activation, were slightly decreased by ectopic expression of Bcl-xL. More strikingly, LPS-induced phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase was strongly repressed by Bcl-xL overexpression, offering a possible mechanism for the inhibition of LPS-induced cytokine production. These data provide the first evidence for a novel role for Bcl-xL as an anti-inflammatory mediator in macrophages. |
| 巻・号 | 165(5) |
| ページ | 2729-37 |
| 公開日 | 2000-9-1 |
| DOI | 10.4049/jimmunol.165.5.2729 |
| PII | ji_v165n5p2729 |
| PMID | 10946304 |
| MeSH | Animals Apoptosis / drug effects Apoptosis / immunology Biological Transport / immunology Cell Line Clone Cells Cytokines / antagonists & inhibitors* Cytokines / biosynthesis* Cytokines / genetics Cytokines / metabolism DNA-Binding Proteins / antagonists & inhibitors DNA-Binding Proteins / metabolism Gene Expression Regulation / drug effects Gene Expression Regulation / immunology Gliotoxin / pharmacology I-kappa B Proteins* Immunosuppressive Agents / pharmacology* Lipopolysaccharides / antagonists & inhibitors Lipopolysaccharides / pharmacology* Macrophages / cytology Macrophages / immunology* Macrophages / metabolism* Mice Mitogen-Activated Protein Kinase 8 Mitogen-Activated Protein Kinases / antagonists & inhibitors Mitogen-Activated Protein Kinases / metabolism NF-KappaB Inhibitor alpha NF-kappa B / antagonists & inhibitors NF-kappa B / metabolism Phosphorylation Protein Processing, Post-Translational / immunology Proto-Oncogene Proteins c-bcl-2 / biosynthesis Proto-Oncogene Proteins c-bcl-2 / genetics Proto-Oncogene Proteins c-bcl-2 / physiology* RNA, Messenger / antagonists & inhibitors RNA, Messenger / biosynthesis RNA, Messenger / metabolism Transcription Factor AP-1 / antagonists & inhibitors Transcription Factor AP-1 / metabolism Transcriptional Activation / immunology Transfection Tumor Necrosis Factor-alpha / antagonists & inhibitors Tumor Necrosis Factor-alpha / biosynthesis Tumor Necrosis Factor-alpha / genetics bcl-X Protein p38 Mitogen-Activated Protein Kinases |
| IF | 4.886 |
| 引用数 | 23 |
| WOS 分野 | IMMUNOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |