Atorvastatin promotes human monocyte differentiation toward alternative M2 macrophages through p38 mitogen-activated protein kinase-dependent peroxisome proliferator-activated receptor γ activation

International Immunopharmacology
Ou Zhang, Jinying Zhang

Abstract

M1 and M2 macrophages are detectable in human atherosclerotic lesions, and M2 macrophages are present at locations distant from the lipid core in more stable zones of the plaque and appear to exert anti-inflammatory properties on M1 macrophages. Peroxisome proliferator-activated receptor (PPAR) γ promotes the differentiation of monocytes into anti-inflammatory M2 macrophages. Although both statins and PPARγ ligands have been reported to protect against the progression of atherosclerosis, no data are currently available regarding the implication of statins in the alternative differentiation of human monocytes. In the present study, we hypothesized that atorvastatin may exert novel effects to prime human monocytes toward an anti-inflammatory alternative M2 phenotype. To this aim, we first found that abundant M2 markers were expressed in human circulating monocytes after atorvastatin treatment. Moreover, atorvastatin was able to induce PPARγ expression and activation in human monocytes in vivo and in vitro, resulting in priming primary human monocytes differentiation into M2 macrophages with a more pronounced paracrine anti-inflammatory activity in M1 macrophages. Additional data with molecular approaches revealed that p38 mitogen...Continue Reading

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Citations

Dec 15, 2017·Journal of Atherosclerosis and Thrombosis·Atsushi Shioi, Yuji Ikari
Mar 8, 2017·Biomedical Materials·Lizette UtomoYvonne M Bastiaansen-Jenniskens
May 26, 2018·International Journal of Molecular Sciences·Gwenaëlle Le Menn, Jaap G Neels
Jun 15, 2017·PloS One·Johanneke J AkershoekMagda M W Ulrich
Jan 27, 2021·Journal of the American Heart Association·Akihiro NakajimaIk-Kyung Jang
Nov 18, 2020·International Journal of Molecular Sciences·Yulong SunYuanyuan Kuang

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