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Atorvastatin ameliorates LPS‐induced inflammatory response by autophagy via AKT/mTOR signaling pathway
Author(s) -
Han Fei,
Xiao QingQing,
Peng Shi,
Che XinYu,
Jiang LiSheng,
Shao Qin,
He Ben
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26320
Subject(s) - autophagy , atorvastatin , pi3k/akt/mtor pathway , atg5 , protein kinase b , ly294002 , inflammation , microbiology and biotechnology , signal transduction , chemistry , proinflammatory cytokine , cancer research , pharmacology , biology , immunology , apoptosis , biochemistry
Macrophages play crucial roles in immune response and atherosclerosis‐related cardiovascular disease. Recent evidence of macrophage autophagy has demonstrated a novel pathway through which contributes to vascular inflammation. The aim of this study was to elucidate the role of autophagy in the inhibition of inflammatory response in macrophages by atorvastatin. We found that atorvastatin promoted autophagy flow determined by up‐regulating the expression of autophagy‐related protein microtubule‐associated protein light chain (LC3B), inducing the formation of autophagosomes and down‐regulating the expression of SQSTM1/P62, which is consumed during autophagy. Atorvastatin also inhibited the expression of inflammatory factors IL‐1β and TNFα induced by LPS in RAW264.7 cells. Furthermore, pretreatment with an autophagy inhibitor 3MA or LY294002 attenuated the suppressive effect of atorvastatin on LPS‐induced IL‐1β and TNFα expression. Additionally, knockdown autophagy‐related gene 5(Atg5) with a special siRNA also prevented the role of atorvastatin in decreasing IL‐1β and TNFα release induced by LPS. Finally, we detected that AKT/mTOR/P70S6K signaling pathway was involved in atorvastatin‐induced autophagy in macrophages. These data suggest that atorvastatin attenuates LPS‐induced inflammatory factors secretion, at least in part, through enhancing autophagy by AKT/mTOR signaling pathway. Our findings provide a novel evidence that statins exert anti‐inflammatory effect in atherosclerosis by autophagy activation.