PMID- 21956776
OWN - NLM
STAT- MEDLINE
DCOM- 20120501
LR  - 20181201
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 113
IP  - 2
DP  - 2012 Feb
TI  - Atorvastatin suppresses inflammatory response induced by oxLDL through inhibition 
      of ERK phosphorylation, IkappaBalpha degradation, and COX-2 expression in murine 
      macrophages.
PG  - 611-8
LID - 10.1002/jcb.23388 [doi]
AB  - Macrophages crosstalk with oxidized low-density lipoprotein (oxLDL), play a 
      critical role in the initiation, progression, and subsequently stability of 
      atherosclerotic plaques. Statins, inhibitors of HMG CoA 
      (3-hydroxy-3-methylglutaryl coenzyme A) reductase, reduce the expression of 
      inflammatory proteins in addition to their lipid-lowering action. However, the 
      effect and detailed anti-inflammation mechanisms of statins in macrophages 
      induced by oxLDL remain unclearly. In the present study, we investigated the 
      effect of atorvastatin on inflammatory response upon oxLDL stimulation in murine 
      macrophages and analyzed the underlying mechanisms. Tumor necrosis factor (TNF)alpha 
      and monocyte chemoattractant protein-1 (MCP-1) mRNA levels were assayed by 
      real-time PCR. The expression of cyclooxygenases-2 (COX-2) was detected by 
      real-time PCR and Western blotting. While mitogen-activated protein kinase (MAPK) 
      phosphorylation and IkappaBalpha degradation were determined by Western blotting. Our 
      results showed that exposure of RAW264.7 cells to oxLDL, substantially changed 
      the morphology of the cells and increased TNFalpha and MCP-1 secretion. While 
      pretreatment with atorvastatin resulted in a significant inhibition of 
      oxLDL-induced morphological alteration and inflammatory cytokines expression in a 
      dose-dependent fashion. Further investigation of the molecular mechanism revealed 
      that oxLDL upregulated the transcription and protein expression of COX-2 in a 
      time-dependent manner. Whereas, pretreatment with atorvastatin suppressed COX-2 
      expression, MAPK activation and IkappaBalpha degradation. Thus, we conclude that the 
      anti-inflammatory effect of atorvastatin is mediated through the inhibition of 
      proinflammatory COX-2. Furthermore, suppression of ERK phosphorylation and IkappaBalpha 
      degradation is involved in this regulation. Our findings provide a novel evidence 
      that statins suppress inflammatory response, exert its anti-atherogenic actions 
      via against inflammation beyond cholesterol-lowing effect.
CI  - Copyright (c) 2011 Wiley Periodicals, Inc.
FAU - Shao, Qin
AU  - Shao Q
AD  - Department of Cardiology, Ren Ji Hospital, Medical School of Shanghai Jiao Tong 
      University, Shanghai, People's Republic of China.
FAU - Shen, Ling-Hong
AU  - Shen LH
FAU - Hu, Liu-Hua
AU  - Hu LH
FAU - Pu, Jun
AU  - Pu J
FAU - Jing, Qing
AU  - Jing Q
FAU - He, Ben
AU  - He B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Chemokines)
RN  - 0 (Heptanoic Acids)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Nfkbia protein, mouse)
RN  - 0 (Pyrroles)
RN  - 0 (oxidized low density lipoprotein)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - A0JWA85V8F (Atorvastatin)
RN  - EC 1.14.99.- (Ptgs2 protein, mouse)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Atorvastatin
MH  - Cell Line
MH  - Cell Shape
MH  - Chemokines/metabolism
MH  - Cyclooxygenase 2/genetics/*metabolism
MH  - Gene Expression
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Heptanoic Acids/*pharmacology
MH  - I-kappa B Proteins/*metabolism
MH  - Inflammation/chemically induced/metabolism
MH  - Lipoproteins, LDL
MH  - MAP Kinase Signaling System/drug effects
MH  - Macrophages/*metabolism/pathology
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 1/*metabolism
MH  - Mitogen-Activated Protein Kinase 3/*metabolism
MH  - NF-KappaB Inhibitor alpha
MH  - Phosphorylation
MH  - Protein Processing, Post-Translational
MH  - Proteolysis/drug effects
MH  - Pyrroles/*pharmacology
EDAT- 2011/10/01 06:00
MHDA- 2012/05/02 06:00
CRDT- 2011/09/30 06:00
PHST- 2011/09/30 06:00 [entrez]
PHST- 2011/10/01 06:00 [pubmed]
PHST- 2012/05/02 06:00 [medline]
AID - 10.1002/jcb.23388 [doi]
PST - ppublish
SO  - J Cell Biochem. 2012 Feb;113(2):611-8. doi: 10.1002/jcb.23388.