PMID- 19167076
OWN - NLM
STAT- MEDLINE
DCOM- 20090622
LR  - 20210102
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 46
IP  - 6
DP  - 2009 Mar
TI  - Beta2-adrenergic receptor regulate Toll-like receptor 4-induced late-phase 
      NF-kappaB activation.
PG  - 1195-203
LID - 10.1016/j.molimm.2008.11.005 [doi]
AB  - Stimulation of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) triggers 
      myeloid differentiation factor 88 (MyD88)-dependent early-phase NF-kappaB 
      activation and Toll/IL-1 receptor domain-containing adaptor-inducing IFN-beta 
      (TRIF)-dependent late-phase NF-kappaB activation. In a previous study, we have 
      shown that beta(2)-adrenergic receptor (beta(2)AR) functions as a negative 
      regulator of NF-kappaB activation through beta-arrestin 2 in the macrophage cell 
      line RAW264 and that down-regulation of beta(2)AR expression in response to LPS 
      is essential for NF-kappaB activation and expression of its target gene, 
      inducible nitric oxide synthase (NOS II). Here, we demonstrate that beta(2)AR 
      plays an important role in TRIF-dependent late-phase NF-kappaB activation. 
      LPS-stimulated down-regulation was induced in MyD88-knockdown cells, but not in 
      TRIF-knockdown cells, suggesting that beta(2)AR expression was down-regulated by 
      the TRIF-dependent pathway. On the other hand, depletion of beta(2)AR or 
      beta-arrestin 2 expression by siRNA decreased cytoplasmic IkappaB alpha and 
      abrogated late-phase IkappaB alpha degradation and NF-kappaB activation in 
      response to LPS. Inducible nitric oxide synthase (NOS II) expression was 
      increased continuously during 24 h of LPS stimulation in control cells, but 
      decreased in beta(2)AR or beta-arrestin 2-knockdown cells after 6 h of LPS 
      stimulation. These findings suggest that beta(2)AR functions not only as a 
      negative regulator of NF-kappaB activation, but also as a stabilizing factor of 
      the NF-kappaB/IkappaB alpha complex through cytoplasmic beta-arrestin 2, and that 
      TRIF-dependent down-regulation of beta(2)AR expression increases the level of 
      cytoplasmic NF-kappaB/IkappaB alpha complex free from beta-arrestin 2, leading to 
      continuous late-phase NF-kappaB activation.
FAU - Kizaki, Takako
AU  - Kizaki T
AD  - Department of Molecular Predictive Medicine and Sport Science, Kyorin University, 
      School of Medicine, Mitaka 181-8611, Japan. kizaki@kyorin-u.ac.jp
FAU - Shirato, Ken
AU  - Shirato K
FAU - Sakurai, Takuya
AU  - Sakurai T
FAU - Ogasawara, Jun-etsu
AU  - Ogasawara JE
FAU - Oh-ishi, Shuji
AU  - Oh-ishi S
FAU - Matsuoka, Takeshi
AU  - Matsuoka T
FAU - Izawa, Tetsuya
AU  - Izawa T
FAU - Imaizumi, Kazuhiko
AU  - Imaizumi K
FAU - Haga, Shukoh
AU  - Haga S
FAU - Ohno, Hideki
AU  - Ohno H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090122
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Arrb2 protein, mouse)
RN  - 0 (Arrestins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Adrenergic, beta-2)
RN  - 0 (TICAM-1 protein, mouse)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (beta-Arrestin 2)
RN  - 0 (beta-Arrestins)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
SB  - IM
MH  - Adaptor Proteins, Vesicular Transport/immunology/metabolism
MH  - Animals
MH  - Arrestins/genetics/immunology/metabolism
MH  - Cell Line
MH  - Down-Regulation
MH  - Gene Knockdown Techniques
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/metabolism
MH  - Mice
MH  - Myeloid Differentiation Factor 88/genetics
MH  - NF-kappa B/*metabolism
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Receptors, Adrenergic, beta-2/immunology/*physiology
MH  - Signal Transduction
MH  - Toll-Like Receptor 4/immunology/*physiology
MH  - beta-Arrestin 2
MH  - beta-Arrestins
EDAT- 2009/01/27 09:00
MHDA- 2009/06/23 09:00
CRDT- 2009/01/27 09:00
PHST- 2008/09/08 00:00 [received]
PHST- 2008/10/15 00:00 [revised]
PHST- 2008/11/16 00:00 [accepted]
PHST- 2009/01/27 09:00 [entrez]
PHST- 2009/01/27 09:00 [pubmed]
PHST- 2009/06/23 09:00 [medline]
AID - S0161-5890(08)00756-6 [pii]
AID - 10.1016/j.molimm.2008.11.005 [doi]
PST - ppublish
SO  - Mol Immunol. 2009 Mar;46(6):1195-203. doi: 10.1016/j.molimm.2008.11.005. Epub 
      2009 Jan 22.