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Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Cell volume restriction by mercury chloride reduces M1-like inflammatory response of bone marrow-derived macrophages
Yen-Chieh Chuang1, Shu-Yu Wu2, Yu-Chuan Huang3,4
1Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
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.
Insights
Aquaporin (AQP) inhibition using mercury chloride (HgCl2) suppressed pro-inflammatory macrophage polarization. This AQP inhibitor reduced cell size changes and inflammatory signaling, promoting autophagy for mitochondrial repair.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Macrophage polarization into M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes is critical in inflammatory diseases.
- Aquaporins (AQPs) are implicated in cell volume regulation and inflammatory responses.
Purpose of the Study:
- To investigate the role of AQPs in macrophage polarization using the AQP inhibitor mercury chloride (HgCl2).
- To elucidate the molecular mechanisms underlying HgCl2's effects on macrophage polarization.
Main Methods:
- Bone marrow-derived macrophages were stimulated with lipopolysaccharides (LPSs).
- AQP expression (AQP-1, AQP-9) and cell size changes were monitored.
- The effects of HgCl2 on macrophage polarization, NF-κB and p38 MAPK pathways, IL-1β production, mitochondrial activity, reactive oxygen species (ROS) production, and autophagy were assessed.
Main Results:
- LPSs increased AQP-1 and AQP-9 expression and cell size.
- HgCl2 abolished LPS-induced cell size changes and suppressed M1 polarization.
- HgCl2 inhibited NF-κB and p38 MAPK activation, reducing IL-1β production.
- HgCl2 attenuated LPS-induced mitochondrial activation and ROS production.
- HgCl2 promoted autophagy, indicated by increased LC3-II/LC3-I ratio and decreased PINK1 expression, suggesting mitochondrial recycling and restoration.
Conclusions:
- The AQP inhibitor HgCl2 suppresses M1 macrophage polarization.
- HgCl2 exerts its effects by restricting cell volume changes, inhibiting the p38 MAPK/NFκB pathway, and promoting autophagy.
- These findings suggest a potential therapeutic mechanism for AQP inhibition in inflammatory conditions.
