PMID- 20465566
OWN - NLM
STAT- MEDLINE
DCOM- 20100826
LR  - 20211020
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Print)
IS  - 0019-2805 (Linking)
VI  - 130
IP  - 3
DP  - 2010 Jul
TI  - Beta-arrestin 2 negatively regulates sepsis-induced inflammation.
PG  - 344-51
LID - 10.1111/j.1365-2567.2009.03185.x [doi]
AB  - Beta-arrestins 1 and 2 are ubiquitously expressed proteins that alter signalling 
      by G-protein-coupled receptors. beta-arrestin 2 plays an important role as a 
      signalling adaptor and scaffold in regulating cellular inflammatory responses. We 
      hypothesized that beta-arrestin 2 is a critical modulator of inflammatory 
      response in experimental sepsis. beta-arrestin 2(-/-) and wild-type (WT) mice 
      were subjected to caecal ligation and puncture (CLP). The survival rate was 
      significantly decreased (P < 0.05) in beta-arrestin 2(-/-) mice (13% survival) 
      compared with WT mice (53% survival). A second group of mice were killed 18 hr 
      after CLP for blood, peritoneal lavage and tissue sample collection. CLP-induced 
      plasma interleukin (IL)-6 was significantly increased 25 +/- 12 fold and caecal 
      myeloperoxidase (MPO) activity was increased 2.4 +/- 0.3 fold in beta-arrestin 
      2(-/-) compared with WT mice. beta-arrestin 2(-/-) mice exhibited more severe 
      lung damage and higher bacterial loads compared with WT mice post CLP challenge 
      as measured by histopathology and colony-forming unit count. In subsequent 
      experiments, splenocytes, peritoneal macrophages and bone marrow-derived 
      macrophages (BMDMs) were isolated and cultured from beta-arrestin 2(-/-) and WT 
      mice and stimulated in vitro with lipopolysaccharide (LPS). Tumour necrosis 
      factor (TNF)-alpha, IL-6 and IL-10 production induced by LPS was significantly 
      augmented (2.2 +/- 0.2 fold, 1.8 +/- 0.1 fold, and 2.2 +/- 0.4 fold, 
      respectively; P < 0.05) in splenocytes from beta-arrestin 2(-/-) mice compared 
      with WT mice. The splenocyte response was different from that of peritoneal 
      macrophages or BMDMs, which exhibited no difference in TNF-alpha and IL-6 
      production upon LPS stimulation between WT and beta-arrestin 2(-/-) mice. Our 
      data demonstrate that beta-arrestin 2 functions to negatively regulate the 
      inflammatory response in polymicrobial sepsis.
FAU - Fan, Hongkuan
AU  - Fan H
AD  - Department of Neurosciences, Medical University of South Carolina, Charleston, 
      SC, USA. fanhong@musc.edu
FAU - Bitto, Alessandra
AU  - Bitto A
FAU - Zingarelli, Basilia
AU  - Zingarelli B
FAU - Luttrell, Louis M
AU  - Luttrell LM
FAU - Borg, Keith
AU  - Borg K
FAU - Halushka, Perry V
AU  - Halushka PV
FAU - Cook, James A
AU  - Cook JA
LA  - eng
GR  - KL2 RR029880/RR/NCRR NIH HHS/United States
GR  - R01 DK055524/DK/NIDDK NIH HHS/United States
GR  - R01 GM027673/GM/NIGMS NIH HHS/United States
GR  - R01 GM067202/GM/NIGMS NIH HHS/United States
GR  - GM27673/GM/NIGMS NIH HHS/United States
GR  - R03 AI079248/AI/NIAID NIH HHS/United States
GR  - DK55524/DK/NIDDK NIH HHS/United States
GR  - R56 DK055524/DK/NIDDK NIH HHS/United States
GR  - AI079248/AI/NIAID NIH HHS/United States
GR  - UL1 RR029882/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100504
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Arrb2 protein, mouse)
RN  - 0 (Arrestins)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (beta-Arrestin 2)
RN  - 0 (beta-Arrestins)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 1.11.1.7 (Peroxidase)
SB  - IM
MH  - Animals
MH  - Arrestins/genetics/*metabolism
MH  - Blood/microbiology
MH  - Cecum/enzymology
MH  - Inflammation/*etiology/genetics/immunology/*metabolism
MH  - Interleukin-10/metabolism
MH  - Interleukin-6/blood/metabolism
MH  - Liver/enzymology/pathology
MH  - Lung/microbiology/pathology
MH  - Macrophages/metabolism
MH  - Macrophages, Peritoneal/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Peritoneal Cavity/microbiology
MH  - Peroxidase/metabolism
MH  - Sepsis/*complications/genetics/*metabolism/pathology
MH  - Spleen/cytology/metabolism
MH  - Survival Analysis
MH  - T-Lymphocytes/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - beta-Arrestin 2
MH  - beta-Arrestins
PMC - PMC2913214
EDAT- 2010/05/15 06:00
MHDA- 2010/08/27 06:00
PMCR- 2011/07/01
CRDT- 2010/05/15 06:00
PHST- 2010/05/15 06:00 [entrez]
PHST- 2010/05/15 06:00 [pubmed]
PHST- 2010/08/27 06:00 [medline]
PHST- 2011/07/01 00:00 [pmc-release]
AID - IMM3185 [pii]
AID - 10.1111/j.1365-2567.2009.03185.x [doi]
PST - ppublish
SO  - Immunology. 2010 Jul;130(3):344-51. doi: 10.1111/j.1365-2567.2009.03185.x. Epub 
      2010 May 4.