Binger, Katrina J. and Gebhardt, Matthias and Heinig, Matthias and Rintisch, Carola and Schroeder, Agnes and Neuhofer, Wolfgang and Hilgers, Karl and Manzel, Arndt and Schwartz, Christian and Kleinewietfeld, Markus and Voelkl, Jakob and Schatz, Valentin and Linker, Ralf A. and Lang, Florian and Voehringer, David and Wright, Mark D. and Hubner, Norbert and Dechend, Ralf and Jantsch, Jonathan and Titze, Jens and Mueller, Dominik N. (2015) High salt reduces the activation of IL-4-and IL-13-stimulated macrophages. JOURNAL OF CLINICAL INVESTIGATION, 125 (11). pp. 4223-4238. ISSN 0021-9738, 1558-8238
Full text not available from this repository. (Request a copy)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(lL-4+IL-13) activation was not associated with increased polarization toward a proinflammatory M1 phenotype. In vitro, high salt decreased the ability of M(lL-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PATHOGENIC T(H)17 CELLS; BLOOD-PRESSURE; T-CELLS; ALTERNATIVE ACTIVATION; TRANSCRIPTION FACTOR; POTASSIUM EXCRETION; GENE-EXPRESSION; DENDRITIC CELLS; M2 MACROPHAGES; URINARY SODIUM; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 May 2019 13:16 |
| Last Modified: | 07 May 2019 13:16 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4548 |
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