Volume 27 Issue 10
Oct.  2014
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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
Citation: 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

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

doi: 10.3967/bes2014.114
Funds:  National Natural Science Foundation of China(81270212)%Natural Science Foundation of Guangdong Province(S2013010014011)%Young Teacher Key Support Project by Sun Yat-Sen University
  • 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.
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Atorvastatin Attenuates TNF-alpha Production via Heme Oxygenase-1 Pathway in LPS-stimulated RAW264.7 Macrophages

doi: 10.3967/bes2014.114
Funds:  National Natural Science Foundation of China(81270212)%Natural Science Foundation of Guangdong Province(S2013010014011)%Young Teacher Key Support Project by Sun Yat-Sen University

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
Citation: 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

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