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Salt increases monocyte CCR2 expression and inflammatory responses in humans
Eliane F.E. Wenstedt, … , Liffert Vogt, Jan Van den Bossche
Eliane F.E. Wenstedt, … , Liffert Vogt, Jan Van den Bossche
Published November 1, 2019
Citation Information: JCI Insight. 2019;4(21):e130508. https://doi.org/10.1172/jci.insight.130508.
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Research Article Clinical trials Inflammation

Salt increases monocyte CCR2 expression and inflammatory responses in humans

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Abstract

Inflammation may play a role in the link between high salt intake and its deleterious consequences. However, it is unknown whether salt can induce proinflammatory priming of monocytes and macrophages in humans. We investigated the effects of salt on monocytes and macrophages in vitro and in vivo by performing a randomized crossover trial in which 11 healthy human subjects adhered to a 2-week low-salt and high-salt diet. We demonstrate that salt increases monocyte expression of CCR2, a chemokine receptor that mediates monocyte infiltration in inflammatory diseases. In line with this, we show a salt-induced increase of plasma MCP-1, transendothelial migration of monocytes, and skin macrophage density after high-salt diet. Macrophages demonstrate signs of an increased proinflammatory phenotype after salt exposure, as represented by boosted LPS-induced cytokine secretion of IL-6, TNF, and IL-10 in vitro, and by increased HLA-DR expression and decreased CD206 expression on skin macrophages after high-salt diet. Taken together, our data open up the possibility for inflammatory monocyte and macrophage responses as potential contributors to the deleterious effects of high salt intake.

Authors

Eliane F.E. Wenstedt, Sanne G.S. Verberk, Jeffrey Kroon, Annette E. Neele, Jeroen Baardman, Nike Claessen, Özge T. Pasaoglu, Emma Rademaker, Esmee M. Schrooten, Rosa D. Wouda, Menno P.J. de Winther, Jan Aten, Liffert Vogt, Jan Van den Bossche

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Figure 4

High salt increases CCR2 expression and transendothelial migration of monocytes in vitro.

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High salt increases CCR2 expression and transendothelial migration of mo...
(A and B) Monocytes of independent healthy donors were stimulated for 24 h in RPMI + 10% FCS + 1% PenStrep in the presence of normal salt (NS), high salt (HS), or 80 mM urea as tonicity control. Then, CCR2 gene expression was assessed with qPCR (A) and protein expression with flow cytometry (B). (C and D) After 24-h incubation in NS, HS, or urea, monocytes were added to the monolayer of cultured human arterial endothelial cells. Transmigrated monocytes (red arrows) were distinguished from adhered monocytes by their transitions from bright to black morphology. NS, ([Na+] = 139 mM); HS, ([Na+] = 179 mM). Values represent mean ± SEM of n = 4 (A and B) and n = 5 (C) healthy donors. Data tested using 1-way ANOVA. **P < 0.01; ***P < 0.001; ****P < 0.0001.

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