Atorvastatin attenuates IL-6 production partly via activating heme oxygenase-1 in LPS-stimulated RAW264.7 macrophages

【摘要】 Background Statins are known as a lipid-lowering drug as well as anti-inflammatory effect, this article aimed to evaluate the effect of atorvastatin on LPS-induced interleukin-6 (IL-6) production and determine the related mechanisms in RAW264.7 macrophages. Methods The levels of IL-6 were determined by enzyme linked immunosorbent assay (ELISA). The levels of mRNA and protein expression of IL-6 and heme oxygenase-1 (HO-1) were respectively determined by quantitative PCR and western-blot. Results LPS could significantly increase mRNA expression of IL-6 and its secretion in dose- and time-dependent manners, which could be significantly attenuated by atorvastatin. In addition, HO-1 expression could be significantly increased by atorvastatin treatment, and it could be remarkably attenuated by SB203580 and PD98059 but not SP600125, which suggests that extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) pathways participate in regulating the above-mentioned effects of atorvastatin on HO-1 expression. In addition, SnPP, a kind of HO-1 activity inhibitor could significantly attenuate atorvastatin’s effects on IL-6 expression and secretion in LPS-stimulated RAW264.7 macrophages. Conclusions Atorvastatin can attenuate LPS-induced IL-6 expression and secretion by activating HO-1 via ERK and p38 MAPK pathways, which helps to explain atorvastatin has pleiotropic benefits for the treatment of diseases associated with inflammation.更多还原

【Abstract】 Background Statins are known as a lipid-lowering drug as well as anti-inflammatory effect, this article aimed to evaluate the effect of atorvastatin on LPS-induced interleukin-6 (IL-6) production and determine the related mechanisms in RAW264.7 macrophages. Methods The levels of IL-6 were determined by enzyme linked immunosorbent assay (ELISA). The levels of mRNA and protein expression of IL-6 and heme oxygenase-1 (HO-1) were respectively determined by quantitative PCR and western-blot. Results LPS could significantly increase mRNA expression of IL-6 and its secretion in dose- and time-dependent manners, which could be significantly attenuated by atorvastatin. In addition, HO-1 expression could be significantly increased by atorvastatin treatment, and it could be remarkably attenuated by SB203580 and PD98059 but not SP600125, which suggests that extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) pathways participate in regulating the above-mentioned effects of atorvastatin on HO-1 expression. In addition, SnPP, a kind of HO-1 activity inhibitor could significantly attenuate atorvastatin’s effects on IL-6 expression and secretion in LPS-stimulated RAW264.7 macrophages. Conclusions Atorvastatin can attenuate LPS-induced IL-6 expression and secretion by activating HO-1 via ERK and p38 MAPK pathways, which helps to explain atorvastatin has pleiotropic benefits for the treatment of diseases associated with inflammation.更多还原