Atorvastatin Attenuates TNF-alpha Production via Heme Oxygenase-1 Pathway in LPS-stimulated RAW264.7 Macrophages.

Xiao Qiao Wang; Nian Sang Luo; Zhong Qing Chen Salah; Yong Qing Lin; Miao Ning GU; Yang Xin Chen

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Atorvastatin Attenuates TNF-alpha Production via Heme Oxygenase-1 Pathway in LPS-stimulated RAW264.7 Macrophages.

Author: Xiao Qiao WANG ^{1
,

2} ; Nian Sang LUO ³ ; Zhong Qing Chen SALAH ⁴ ; Yong Qing LIN ³ ; Miao Ning GU ⁵ ; Yang Xin CHEN ³ ;
Author Information

1. Department of Anesthesiology, Nanfang Hospital of Southern Medical University, Guangzhou 510515, Guangdong, China
2. Department of Anesthesiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong, China.
3. Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou 510120, Guangdong, China
4. Department of Surgery Intensive Care Unit, Nanfang Hospital of Southern Medical University, Guangzhou 510515, Guangdong, China.
5. Department of Anesthesiology, Nanfang Hospital of Southern Medical University, Guangzhou 510515, Guangdong, China.
Publication Type:Journal Article
Keywords: Atorvastatin; Heme oxygenase-1; Lipopolysaccharide; Tumor necrosis factor-α
MeSH: Adjuvants, Immunologic; pharmacology; Animals; Atorvastatin Calcium; Enzyme Activation; drug effects; Heme Oxygenase-1; genetics; metabolism; Heptanoic Acids; pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors; pharmacology; Lipopolysaccharides; pharmacology; Macrophages; drug effects; Membrane Proteins; genetics; metabolism; Mice; Pyrroles; pharmacology; Tumor Necrosis Factor-alpha; metabolism
From: Biomedical and Environmental Sciences 2014;27(10):786-793
CountryChina
Language:English
Abstract:
OBJECTIVETo assess the effect of atorvastatin on lipopolysaccharide (LPS)-induced TNF-α production in RAW264.7 macrophages.
METHODSRAW264.7 macrophages were treated in different LPS concentrations or at different time points with or without atorvastatin. TNF-α level in supernatant was measured. Expressions of TNF-α mRNA and protein and heme oxygenase-1 (HO-1) were detected by ELISA, PCR, and Western blot, respectively. HO activity was assayed.
RESULTSLPS significantly increased the TNF-α expression and secretion in a dose- and time-dependent manner. The HO-1 activity and HO-1 expression level were significantly higher after atorvastatin treatment than before atorvastatin treatment and attenuated by SB203580 and PD98059 but not by SP600125, suggesting that the ERK and p38 mitogen-activated protein kinase (MAPK) pathways participate in regulating the above-mentioned effects of atorvastatin. Moreover, the HO-1 activity suppressed by SnPP or the HO-1 expression inhibited by siRNA significantly attenuated the effect of atorvastatin on TNF-α expression and production in LPS-stimulated macrophages.
CONCLUSIONAtorvastatin can attenuate LPS-induced TNF-α expression and production by activating HO-1 via the ERK and p38 MAPK pathways, suggesting that atorvastatin can be used in treatment of inflammatory diseases such as sepsis, especially in those with atherosclerotic diseases.