| 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
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535) |
