科研之友
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摘要
Objective To assess the effect of atorvastatin on lipopolysaccharide (LPS)-induced TNF-alpha production in RAW264.7 macrophages. Methods RAW264.7 macrophages were treated in different LPS concentrations or at different time points with or without atorvastatin. TNF-alpha level in supernatant was measured. Expressions of TNF-alpha mRNA and protein and heme oxygenase-1 (HO-1) were detected by ELISA, PCR, and Western blot, respectively. HO activity was assayed. Results LPS significantly increased the TNF-alpha 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-alpha expression and production in LPS-stimulated macrophages. Conclusion Atorvastatin can attenuate LPS-induced TNF-alpha 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.
