Monotropein inhibits THP-1-derived foam cell formation by regulating macrophage polar-ization
Objective:To investigate the effect of monotropein(MON)on macrophage polarization and the for-mation of THP-1 derived foam cells.Methods:THP-1 cells were incubated with 100 ng/mL phorbol 12-my-ristate 13-acetate(PMA)for 48 hours to induce M0 macrophages,which were identified by flow cytometry.Foam cells were induced by treating macrophages with different concentrations of oxidized low-density lipopro-tein(ox-LDL)(0 μg/mL,25 μg/mL,50 μg/mL,100 μg/mL,150 μg/mL)for different ox-LDL intervention times(0 h,3 h,6 h,12 h,24 h).Macrophages were intervened with ox-LDL or MON,and cell viability was assessed us-ing CCK-8.The experimental groups were divided into control group,ox-LDL group,and ox-LDL+MON group.Oil Red O staining was employed to observe the lipid engulfment of cells in each group.Western blotting and re-verse transcription-quantitative PCR(RT-qPCR)were utilized to evaluate the polarization of macrophages and the outcomes of signaling pathways associated with ferroptosis.Results:The ox-LDL increased iNOS and TNF-α protein expression in a concentration-and time-dependent manner.The ox-LDL significantly reduced cell via-bility,which could significantly be restored by 200 μmol/L MON,but would be decreased when the concentra-tion was up to 1000 μmol/L MON.A large number of obvious ox-LDL-induced intracellular lipid droplets were observed in the cells,and the amount of lipid droplets in the cells were markedly reduced with MON treatment.Compared with the control group,ox-LDL-induced macrophages showed increased CD86 mRNA and iNOS pro-tein expression levels and decreased CD206 mRNA,Arg-1,SLC7A11,and GPX4 protein expression levels,while MON intervention decreased CD86 mRNA and iNOS protein expression levels and increased Arg-1,SLC7A11,and GPX4 protein expression levels(all P＜0.05).Conclusion:MON inhibits ox-LDL-induced foam cell formation and enhances cell viability by reducing M1 polarization and promoting M2 polarization in macro-phages,which may be associated with inhibition of ferroptosis.
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