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

• Published in: Frontiers in pharmacology 2022-12, Vol.13, p.1074986-1074986
• Main Authors: Chuang, Yen-Chieh, Wu, Shu-Yu, Huang, Yu-Chuan, Peng, Chung-Kan, Tang, Shih-En, Huang, Kun-Lun
• Format: Article
• Language: English
• Subjects: aquaporin; autophagy; bone marrow-derived macrophages; macrophage polarization; mercury chloride; Pharmacology
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2022.1074986

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 (HgCl ). 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 HgCl abolished cell size changes and significantly suppressed M1 polarization. HgCl 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. HgCl attenuated LPS-induced activation of mitochondria and reactive oxygen species production and autophagy was promoted by HgCl . 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 HgCl . In summary, the present study demonstrates a possible mechanism of the AQP inhibitor HgCl in macrophage M1 polarization through the restriction of cell volume change, suppression of the p38 MAPK/NFκB pathway, and promotion of autophagy.