LXRα/ABCA1-mediated immunommetabolic remodeling:a novel mechanism of curcumin in enhancing the anti-tuberculosis function of macrophages
10.13431/j.cnki.immunol.j.20250087
- VernacularTitle:LXRα/ABCA1介导的免疫代谢重塑:姜黄素增强巨噬细胞抗结核功能的新机制
- Author:
Bing ZHAO
1
;
Xiaoqun HAN
;
Qin DENG
;
Nanyan FU
;
Zhixing ZHOU
;
Yijing ZHU
Author Information
1. 宜春学院药学院,江西 宜春 336000
- Publication Type:Journal Article
- Keywords:
mycobacterium tuberculosis;
curcumin;
hepatic X receptor α;
ABCA1;
macrophage;
anti-tuberculosis function;
immune metabolism regulation
- From:
Immunological Journal
2025;41(9):618-624
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the molecular mechanism by which curcumin enhances the anti-tuberculosis function of macrophages through immune metabolic regulation mediated by liver X receptor α(LXRα)/ABCA1.Methods A model was established by infecting THP-1-derived macrophages with attenuated strain of Mycobacterium bovis(M.bovis).The control group,curcumin group,M.pavis group,M.pavis+LXRα agonist(T0901317)group,M.pavis+LXRα inhibitor(GSK2033)group,M.pavis+curcumin group,M.pavis+curcumin+GSK2033 group and M.pavis+curcumin+T0901317 group were set up.The protein and gene expressions of LXRα/ABCA1 were detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).The accumulation of lipid droplets was analyzed by Oil Red O staining and micro-assay.The lipid content of the supernatant was determined by a biochemical analyzer,and cell proliferation was assessed by the MTT method.Bacterial clearance capacity was evaluated by measuring intracellular bacterial load.Results Curcumin significantly upregulated the protein and gene expression of LXRα/ABCA1 in M.Bovis-infected macrophages,reduced intracellular lipid accumulation and promoted lipid efflux,while enhancing cell proliferation and reducing intracellular bacterial load(P<0.05,P<0.01).LXRα inhibitors could reverse the effect of curcumin,while agonists synergistically enhanced its effect.Correlation analysis showed that the expression of LXRα/ABCA1 in cells was negatively correlated with the intracellular bacterial load,while the lipid level was positively correlated with the intracellular bacterial load(P<0.01).Conclusion Curcumin activates the LXRα/ABCA1 pathway,coordinates the metabolic remodeling of macrophages and the enhancement of immune function,and forms a synergistic effect against tuberculosis,providing an experimental basis for the development of a novel host-directed treatment strategy for tuberculosis based on immune-metabolic regulation.
