Cell volume restriction by mercury chloride reduces M1-like inflammatory response of bone marrow-derived macrophages

Frontiers in Pharmacology

Pharmacology

Yen-Chieh Chuang¹  Kun-Lun Huang²  Shu-Yu Wu³  Chung-Kan Peng⁴  Shih-En Tang⁴  Yu-Chuan Huang⁵ 

[1] Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan;Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan;Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan;Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan;Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan;Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan;Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan;School of Pharmacy, National Defense Medical Center, Taipei, Taiwan;Department of Research and Development, National Defense Medical Center, Taipei, Taiwan;

关键词: aquaporin;    bone marrow-derived macrophages;    mercury chloride;    macrophage polarization;    autophagy;   

DOI  :  10.3389/fphar.2022.1074986

 received in 2022-10-20, accepted in 2022-11-23,  发布年份 2022

来源: Frontiers

【 摘 要 】

Dysregulation of macrophages in the pro-inflammatory (M1) and anti-inflammatory (M2) sub-phenotypes is a crucial element in several inflammation-related diseases and injuries. We investigated the role of aquaporin (AQP) in macrophage polarization using AQP pan-inhibitor mercury chloride (HgCl2). Lipopolysaccharides (LPSs) induced the expression of AQP-1 and AQP-9 which increased the cell size of bone marrow-derived macrophages. The inhibition of AQPs by HgCl2 abolished cell size changes and significantly suppressed M1 polarization. HgCl2 significantly reduced the activation of the nuclear factor kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) pathways and inhibited the production of IL-1β. HgCl2 attenuated LPS-induced activation of mitochondria and reactive oxygen species production and autophagy was promoted by HgCl2. The increase in the light chain three II/light chain three I ratio and the reduction in PTEN-induced kinase one expression suggests the recycling of damaged mitochondria and the restoration of mitochondrial activity by HgCl2. In summary, the present study demonstrates a possible mechanism of the AQP inhibitor HgCl2 in macrophage M1 polarization through the restriction of cell volume change, suppression of the p38 MAPK/NFκB pathway, and promotion of autophagy.

【 授权许可】

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Copyright © 2022 Chuang, Wu, Huang, Peng, Tang and Huang.