Luteolin Regulates Macrophage Polarization via the PI3K/Akt Pathway to Inhibit the Apoptosis Stimulated by Angiotensin II

BACKGROUND: The aim of this study was to investigate anti-apoptotic effects of luteolin on angiotensin II-stimulated murine peritoneal macrophages and to explore its mechanisms. METHODS AND RESULTS: The viability and cytotoxicity of murine peritoneal macrophages were assessed using the Cell Counting Kit-8 assay and measuring lactate dehydrogenase levels, respectively. Apoptotic rates were determined using Annexin V/propidium iodide staining. Protein expression was examined by western blotting, and markers of macrophage phenotypes were analyzed by flow cytometry and ELISA. Luteolin decreased the apoptotic rate of angiotensin II-stimulated macrophages. This effect was associated with increased Bcl-2 and caspase-3 levels as well as decreased Bax and cleaved caspase-3 levels. Additionally, luteolin reduced the expression of M1 macrophage phenotype markers (IL-6, TNF-α, iNOS, CD16/32) and increased the expression of M2 macrophage phenotype markers (Dectin-1, IL-10, Arg-1, CD206). Moreover, luteolin blocked Akt phosphorylation on residues 308 and 473, which were up-regulated in presence of angiotensin II. The effects of luteolin were similar to those of LY294002, a specific PI3K/Akt pathway inhibitor. CONCLUSIONS: These results indicated that luteolin has anti-apoptotic effects on angiotensin II-stimulated macrophages via macrophage polarization, which might be associated with PI3K/Akt signaling.