Potassium supplementation inhibits IL-17A production induced by salt loading in human T lymphocytes via p38/MAPK-SGK1 pathway

Exp Mol Pathol. 2016 Jun;100(3):370-7. doi: 10.1016/j.yexmp.2016.03.009. Epub 2016 Mar 25.

Abstract

High salt intake contributes to the development of autoimmune/inflammatory diseases, while potassium supplementation antagonizes the effects. Interleukin (IL)-17A are tightly related with autoimmune/inflammatory diseases. Thus, we explored the effects and underlying molecular mechanism of high salt and potassium supplementation on IL-17A production in T lymphocytes. Forty-nine healthy participants received a low-salt, high-salt, followed by a high-salt diet plus potassium supplement for 7 days, respectively. Human T lymphocyte Jurkat cells were treated with different concentrations of NaCl and KCl. In the participants, IL-17A levels in plasma and in peripheral blood mononuclear cells (PBMC) were significantly increased after a high-salt diet, which was dramatically reversed when potassium was supplemented. In Jurkat cells, the addition of 40 mM NaCl markedly enhanced IL-17A production and the expression of phosphorylated p38/mitogen-activated protein kinase (MAPK) and its downstream target, serum/glucocorticoid-regulated kinase (SGK)1, whereas combined treatment with additional 2 mM KCl significantly decreased them. Respective inhibition of p38/MAPK and SGK1 suppressed IL-17A expression induced by NaCl, and KCl inhibited IL-17A production induced by specific activator of p38/MAPK. We conclude potassium supplementation has a blocking effect on IL-17A production in T lymphocytes induced by salt loading. This protective effect is mediated through the direct suppression of p38/MAPK-SGK1 pathway.

Keywords: IL-17A; SGK1; high salt diet; p38/MAPK; potassium supplementation.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blotting, Western
  • Dietary Supplements*
  • Female
  • Gene Expression / drug effects
  • Humans
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism*
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / blood
  • Interleukin-17 / genetics
  • Jurkat Cells
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Phosphorylation / drug effects
  • Potassium / administration & dosage
  • Potassium / pharmacology*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Sodium Chloride / administration & dosage
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • IL17A protein, human
  • Immediate-Early Proteins
  • Interleukin-17
  • Sodium Chloride
  • Protein-Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase
  • p38 Mitogen-Activated Protein Kinases
  • Potassium