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pubmed-article:18194271pubmed:abstractTextToll-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.lld:pubmed
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pubmed-article:18194271pubmed:authorpubmed-author:TaniguchiNaoy...lld:pubmed
pubmed-article:18194271pubmed:authorpubmed-author:TobaKenjiKlld:pubmed
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pubmed-article:18194271pubmed:authorpubmed-author:SakuraiTakuya...lld:pubmed
pubmed-article:18194271pubmed:authorpubmed-author:KizakiTakakoTlld:pubmed
pubmed-article:18194271pubmed:authorpubmed-author:OhnoHidekiHlld:pubmed
pubmed-article:18194271pubmed:authorpubmed-author:IzawaTetsuyaTlld:pubmed
pubmed-article:18194271pubmed:authorpubmed-author:HagaShukohSlld:pubmed
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pubmed-article:18194271pubmed:dateRevised2009-11-18lld:pubmed
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pubmed-article:18194271pubmed:articleTitleBeta2-adrenergic receptor regulates Toll-like receptor-4-induced nuclear factor-kappaB activation through beta-arrestin 2.lld:pubmed
pubmed-article:18194271pubmed:affiliationDepartment of Molecular Predictive Medicine and Sport Science, Kyorin University, School of Medicine, Mitaka, Japan. kizaki@kyorin-u.ac.jplld:pubmed
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