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

Abstract

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.

• Authors: Yen-Chieh Chuang, Shu-Yu Wu, Yu-Chuan Huang, Chung-Kan Peng, Shih-En Tang, Kun-Lun Huang
• Journal: Frontiers in pharmacology (Front Pharmacol) Vol. 13 Pg. 1074986 ( 2022) ISSN: 1663-9812 [Print] Switzerland
• PMID: 36582541 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Chuang, Wu, Huang, Peng, Tang and Huang.