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Luteolin transforms the BMDM polarity to regulate the expression of inflammatory factors

By Shuxia Wang, Shuhang Xu, Meng Cao, Jing Zhou, Xiaodong Mao, Xiaoming Yao, Chao J. Liu

Posted 02 Jul 2020
bioRxiv DOI: 10.1101/2020.06.30.181503

Macrophage are indispensable regulator cells in inflammatory response. Macrophage polarization and its secreted inflammatory factors have affinity with the outcomes of inflammation. Luteolin, a flavonoid abundant in plants has anti-Inflammatory activity, but whether luteolin can manipulate M1/M2 polarization of BMDM to suppress inflammation is still veiled. The purpose of this study was to observe the effects of luterolin on the polarity of BMDM derived from C57BL/6 mice and the expression of inflammatory factors, to explore the mechanism of luteolin regulating the BMDM polarity. M1-polarized BMDM were induced by LPS+IFN-γ, M2-polarization were stimulated with IL-4. BMDM morphology was observed by laser confocal microscopy; levels of BMDM differentiation and CD11c or CD206 on membrane surface were assessed by FCM; mRNA and protein of M1/M2-type inflammatory factors were performed by qPCR and ELISA, respectively; the expression of p-STAT1 and p-STAT6 protein pathways was detected by Western-blotting. The isolated mouse bone marrow cells were successfully differentiated into BMDM, LPS+IFN-γ induced BMDM M1-phenotype polarization, and IL-4 induced its M2-phenotype polarization. After M1-polarized BMDM treated with luteolin, M1-type pro-inflammatory factors including IL-6, TNF-α, iNOS, CD86 were down-regulated while M2-type anti-inflammatory factors including IL-10, Arg1, CD206 were up-regulated; the expression of M1-type surface marker CD11c decreased, nevertheless, M2-type marker CD206 increased; levels of inflammatory signaling protein p-STAT1 and p-STAT6 were attenuated and enhanced respectively. Our study suggests luteolin may transform BMDM polarity through p-STAT1/6 to regulate the expression of inflammatory mediators, thereby inhibiting inflammation. Naturally occurring luteolin hold promise as an anti-inflammatory and immunomodulatory agent.

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