Beta2-adrenergic receptor regulates Toll-like receptor-4-induced nuclear factor-kappaB activation through beta-arrestin 2

Immunology
Takako KizakiHideki Ohno

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 Ikappa...Continue Reading

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Citations

Jul 31, 2009·Pflügers Archiv : European journal of physiology·Ken ShiratoHideki Ohno
Jun 12, 2013·Infection and Immunity·Deepika SharmaNarayanan Parameswaran
Jan 15, 2014·Journal of Neuroinflammation·Iciar GárateJuan Carlos Leza
Jul 19, 2014·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Ren-Wei DuWen-Guang Bu
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Aug 22, 2012·Biological Psychiatry·Iciar GárateJuan Carlos Leza
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May 14, 2008·Biochemical and Biophysical Research Communications·Takako KizakiHideki Ohno
Sep 18, 2015·Genes and Immunity·D Sharma, N Parameswaran
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