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

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Binger KJ, Gebhardt M, Heinig M, Rintisch C, Schröder A, Neuhofer W, Hilgers KF, Manzel A, Schwartz C, Kleinewietfeld M, Voelkl J, Schatz V, Linker R, Lang F, Vöhringer D, Wright MD, Hubner N, Dechend R, Jantsch J, Titze J, Mueller DN
Zeitschrift: Journal of Clinical Investigation
Jahr der Veröffentlichung: 2015
Band: 125
Heftnummer: 11
Seitenbereich: 4223-38
ISSN: 0021-9738


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.



FAU-Autoren / FAU-Herausgeber

Hilgers, Karl Friedrich Prof. Dr. med.
Professur für Innere Medizin (Hochdruckforschung)
Linker, Ralf PD Dr.
Stiftungsprofessur für Neuroimmunologie
Schröder, Agnes Dr. rer. nat.
Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung
Schwartz, Christian
Infektionsbiologische Abteilung am Mikrobiologischen Institut
Titze, Jens Prof. Dr.
Professur für Elektrolyt- und Kreislaufforschung
Vöhringer, David Prof. Dr.
Professur für Infektionsabwehr und Toleranz


Autor(en) der externen Einrichtung(en)
Eberhard Karls Universität Tübingen
Experimental and Clinical Research Center (ECRC)
Max-Delbrück-Centrum für Molekulare Medizin (MDC) Berlin-Buch
Monash University
Technische Universität Dresden
Universitätsklinikum Heidelberg
Universitätsklinikum Regensburg


Zitierweisen

APA:
Binger, K.J., Gebhardt, M., Heinig, M., Rintisch, C., Schröder, A., Neuhofer, W.,... Mueller, D.N. (2015). High salt reduces the activation of IL-4- and IL-13-stimulated macrophages. Journal of Clinical Investigation, 125(11), 4223-38. https://dx.doi.org/10.1172/JCI80919

MLA:
Binger, Katrina J., et al. "High salt reduces the activation of IL-4- and IL-13-stimulated macrophages." Journal of Clinical Investigation 125.11 (2015): 4223-38.

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Zuletzt aktualisiert 2018-09-10 um 07:18