Atorvastatin Attenuates TNF-alpha Production via Heme Oxygenase-1 Pathway in LPS-stimulated RAW264.7 Macrophages
Abstract: ObjectiveTo assess the effect of atorvastatin on lipopolysaccharide(LPS)-inducedTNF-α production in RAW264.7 macrophages. MethodsRAW264.7 macrophageswere treated in different LPS concentrations oratdifferent time points with or without atorvastatin. TNF-α level in supernatant was measured. Expressions of TNF-αmRNA and protein and heme oxygenase-1 (HO-1) were detected by ELISA, PCR, and Western blot, respectively. HOactivity was assayed. ResultsLPS significantly increased the TNF-α expression and secretion in a dose- and time-dependent manner. The HO-1activity 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 inregulating 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 onTNF-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.
|WANG Xiao Qiao, LUO Nian Sang, CHEN Zhong Qing, LIN Yong Qing, GU Miao Ning, CHEN Yang Xin. Atorvastatin Attenuates TNF-alpha Production via Heme Oxygenase-1 Pathway in LPS-stimulated RAW264.7 Macrophages[J]. Biomedical and Environmental Sciences, 2014, 27(10): 786-793. doi: 10.3967/bes2014.114