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High salt reduces the activation of IL-4- and IL-13-stimulated macrophages

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Item Type:Article
Title:High salt reduces the activation of IL-4- and IL-13-stimulated macrophages
Creators Name:Binger, K.J. and Gebhardt, M. and Heinig, M. and Rintisch, C. and Schroeder, A. and Neuhofer, W. and Hilgers, K. and Manzel, A. and Schwartz, C. and Kleinewietfeld, M. and Voelkl, J. and Schatz, V. and Linker, R.A. and Lang, F. and Voehringer, D. and Wright, M.D. and Hubner, N. and Dechend, R. and Jantsch, J. and Titze, J. and Müller, D.N.
Abstract:A high intake of dietary salt (NaCl) has been implicated in the development of hypertension, chronic inflammation, and autoimmune diseases. We have recently shown that salt has a proinflammatory effect and boosts the activation of Th17 cells and the activation of classical, LPS-induced macrophages (M1). Here, we examined how the activation of alternative (M2) macrophages is affected by salt. In stark contrast to Th17 cells and M1 macrophages, high salt blunted the alternative activation of BM-derived mouse macrophages stimulated with IL-4 and IL-13, M(IL-4+IL-13) macrophages. Salt-induced reduction of M(IL-4+IL-13) activation was not associated with increased polarization toward a proinflammatory M1 phenotype. In vitro, high salt decreased the ability of M(IL-4+IL-13) macrophages to suppress effector T cell proliferation. Moreover, mice fed a high salt diet exhibited reduced M2 activation following chitin injection and delayed wound healing compared with control animals. We further identified a high salt-induced reduction in glycolysis and mitochondrial metabolic output, coupled with blunted AKT and mTOR signaling, which indicates a mechanism by which NaCl inhibits full M2 macrophage activation. Collectively, this study provides evidence that high salt reduces noninflammatory innate immune cell activation and may thus lead to an overall imbalance in immune homeostasis.
Keywords:Bone Marrow Cells, Cultured Cells, Chitin, Dietary Sodium Chloride, Gene Expression Regulation, Glycolysis, Histone Code, Inbred C57BL Mice, Inflammation, Innate Immunity, Interleukin-13, Interleukin-4, Macrophage Activation, Macrophages, Mitochondria, Oxidative Phosphorylation, Proto-Oncogene Proteins c-akt, Random Allocation, Signal Transduction, Sodium Chloride, TOR Serine-Threonine Kinases, Transgenic Mice, Wound Healing, Animals, Mice
Source:Journal of Clinical Investigation
Publisher:American Society for Clinical Investigation
Page Range:4223-4238
Date:2 November 2015
Additional Information:Copyright © 2015, American Society for Clinical Investigation
Official Publication:https://doi.org/10.1172/JCI80919
PubMed:View item in PubMed

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