論文 - 詳細
| RRC ID | 6562 |
|---|---|
| 著者 | Kizaki T, Izawa T, Sakurai T, Haga S, Taniguchi N, Tajiri H, Watanabe K, Day NK, Toba K, Ohno H. |
| タイトル | Beta2-adrenergic receptor regulates Toll-like receptor-4-induced nuclear factor-kappaB activation through beta-arrestin 2. |
| ジャーナル | Immunology |
| Abstract |
Toll-like receptors (TLRs) play an important role in innate immunity while, beta(2)-adrenergic receptors (beta(2)AR) provide the key linkages for the sympathetic nervous system to regulate the immune system. However, their role in macrophages remains uncertain. Here, we demonstrate the cross-talk between beta(2)AR and TLR signalling pathways. Expression of beta(2)AR was down-regulated by TLR4 ligand lipopolysaccharide (LPS) stimulation. To investigate the physiological consequence of this down-regulation RAW264 cells, a macrophage cell line, were transfected with a beta(2)AR expression vector (RAWar). Both LPS-stimulated inducible nitric oxide synthase (NOS II) expression and NO production were markedly suppressed in the RAWar cells. The activation of nuclear factor-kappaB (NF-kappaB) and degradation of the inhibitor of NF-kappaB (IkappaBalpha) in response to LPS were markedly decreased in these cells. The level of beta-arrestin 2, which regulates beta(2)AR signalling, was also reduced in RAW264 cells after stimulation with LPS, but not in RAWar cells. Overexpression of beta-arrestin 2 (RAWarr2) also inhibited NO production and NOS II expression. Furthermore, we demonstrated that beta-arrestin 2 interacted with cytosolic IkappaBalpha and that the level of IkappaBalpha coimmunoprecipitated by anti-beta-arrestin 2 antibodies was decreased in the RAW264 cells but not in RAWar or RAWarr2 cells. These findings suggest that LPS-stimulated signals suppress beta(2)AR expression, leading to down-regulation of beta-arrestin 2 expression, which stabilizes cytosolic IkappaBalpha and inhibits the NF-kappaB activation essential for NOS II expression, probably to ensure rapid and sufficient production of NO in response to microbial attack. |
| 巻・号 | 124(3) |
| ページ | 348-56 |
| 公開日 | 2008-7-1 |
| DOI | 10.1111/j.1365-2567.2007.02781.x |
| PII | IMM2781 |
| PMID | 18194271 |
| PMC | PMC2440829 |
| MeSH | Animals Arrestins / immunology* Cell Line Down-Regulation / immunology Electrophoretic Mobility Shift Assay Lipopolysaccharides / immunology Macrophages / immunology* Mice NF-kappa B / metabolism* Nitric Oxide Synthase Type II / metabolism Receptors, Adrenergic, beta-2 / immunology* Signal Transduction / immunology Toll-Like Receptor 4 / immunology* beta-Arrestin 2 beta-Arrestins |
| IF | 5.016 |
| 引用数 | 34 |
| WOS 分野 | IMMUNOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |