出版社：American Society for Biochemistry and Molecular Biology
摘要：Interleukin (IL)-10 may have a therapeutic potential in atherosclerosis, but its mechanisms of action have not been clarified. Foam cell formation is a key event in atherogenesis, and apoptosis of these lipid-laden cells may promote plaque destabilization. We sought to explore whether IL-10 could have plaque-stabilizing properties in acute coronary syndromes (ACS). We studied the effect of IL-10 on oxidized low density lipoprotein (oxLDL)-stimulated THP-1 cells and monocyte-derived macrophages from ACS patients and healthy controls using different experimental approaches. Our main findings were: i) IL-10 enhances lipid accumulation in oxLDL-stimulated THP-1 macrophages, at least partly by counteracting oxLDL-induced apoptosis; ii) This antiapoptotic effect of IL-10 involves increased expression of the antiapoptotic genes Bfl-1 and Mcl-1, accompanied by protective effects on mitochondria function; iii) By silencing Bfl-1 and Mcl-1 genes using siRNAs, we were able to abolish this IL-10-mediated effect on lipid accumulation; iv) IL-10 also induced lipid accumulation in oxLDL-stimulated macrophages from patients with ACS, but not in macrophages from healthy controls; v) In ACS patients, this enhancing effect of IL-10 on lipid accumulation was accompanied by enhanced Mcl-1 expression. No such antiapoptotic effect was seen in macrophages from healthy controls.
These findings suggest a new mechanism for the effect of IL-10 in atherosclerosis, possibly contributing to plaque stabilization.
Abbreviations: ACS, acute coronary syndromes; CAD, coronary artery disease; CRP, C-reactive protein; IL, interleukin; LOX-1, lectin-like oxLDL receptor-1; oxLDL, oxidized low density lipoprotein; PBMC, peripheral blood mononuclear cell; PI, propidium iodine; PMA, phorbol myristate acetate; RPA, RNase protection assay; TNF, tumor necrosis factor
