Vitamin D receptor (VDR) on the cell membrane of mouse macrophages participates in the formation of lipopolysaccharide tolerance: mVDR is related to the effect of artesunate to reverse LPS tolerance

Author:

Zhang Yu,Zhou Jun,Hua Ling,Li Pan,Wu Jiaqi,Shang Shenglan,Deng Fei,Luo Jing,Liao Mengling,Wang Nuoyan,Pan Xichun,Yuan Yue,Zheng Yue,Lu Yonglin,Huang Yasi,Zheng Jiang,Liu Xin,Li Xiaoli,Zhou Hong

Abstract

AbstractIt is unclear whether membrane vitamin D receptor (mVDR) exists on the macrophage membrane or whether mVDR is associated with lipopolysaccharide (LPS) tolerance. Herein, we report that interfering with caveolae and caveolae-dependent lipid rafts inhibited the formation of LPS tolerance. VDR was detected as co-localized with membrane molecular markers. VDR was detected on the cell membrane and its level was higher in LPS-tolerant cells than that in only LPS treatment cells. Anti-VDR antibodies could abolish the effect of artesunate (AS) to reverse LPS tolerance, and the wild-type peptides (H397 and H305) of VDR, but not the mutant peptide (H397D and H305A), led to the loss of AS’s effect. AS decreased the mVDR level in LPS-tolerant cells. In vivo, AS significantly reduced VDR level in the lung tissue of LPS-tolerant mice. In summary, mVDR exists on the cell membrane of macrophages and is closely associated with the formation of LPS tolerance and the effects of AS.

Funder

Hong Zhou

Publisher

Springer Science and Business Media LLC

Subject

Cell Biology,Molecular Biology,Biochemistry

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