2. Academic Validation
  3. 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

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

  • Cell Commun Signal. 2023 May 29;21(1):124. doi: 10.1186/s12964-023-01137-w.
Yu Zhang # 1,  Jun Zhou # 1,  Ling Hua # 1,  Pan Li # 2,  Jiaqi Wu 3,  Shenglan Shang 3,  Fei Deng 1,  Jing Luo 1,  Mengling Liao 1,  Nuoyan Wang 1,  Xichun Pan 2,  Yue Yuan 1,  Yue Zheng 3,  Yonglin Lu 3,  Yasi Huang 1,  Jiang Zheng 3,  Xin Liu 4,  Xiaoli Li 5 6,  Hong Zhou 7
Affiliations

Affiliations

  • 1 Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, 563000, China.
  • 2 Department of Pharmacology, College of Pharmacy, Army Medical University (Third Military Medical University), Chongqing, 400038, PR China.
  • 3 Medical Research Centre, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.
  • 4 Medical Research Centre, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, PR China. triplestars@163.com.
  • 5 Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, PR China. plum181181@126.com.
  • 6 Chongqing Key Laboratory of Drug Metabolism, Chongqing, 400016, China. plum181181@126.com.
  • 7 Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, 563000, China. zhouh64@163.com.
  • # Contributed equally.
PMID: 37248534 DOI: 10.1186/s12964-023-01137-w
Abstract

It 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. Video Abstract.

Keywords

Artesunate; Caveolin-1; LPS tolerance; Lipid raft; Membrane vitamin D receptor.

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