title: Potassium supplementation inhibits IL-17A production induced by salt loading in human T lymphocytes via p38/MAPK-SGK1 pathway.
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.
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wen
authors.affiliation: Department of Cardiovascular Medicine, Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Zhaofei
authors.initials: Z
authors.lastname: Wan
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Keyu
authors.initials: K
authors.lastname: Ren
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Qiyue
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, China; Shaanxi Key Laboratory of Molecular Cardiology, Xi'an, China. Electronic address: zuyiyuan@mail.xjtu.edu.cn.
authors.forename: Zuyi
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, China; Shaanxi Key Laboratory of Molecular Cardiology, Xi'an, China. Electronic address: 1306899042@qq.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000328:Adult; D015153:Blotting, Western; D019587:Dietary Supplements; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D011188:Potassium / Q000008:administration & dosage / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D012965:Sodium Chloride / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D017874:Immediate-Early Proteins; D020381:Interleukin-17; D011188:Potassium; D017346:Protein Serine-Threonine Kinases; D012965:Sodium Chloride; D048051:p38 Mitogen-Activated Protein Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases; C508717:IL17A protein, human
keywords: IL-17A; SGK1; high salt diet; p38/MAPK; potassium supplementation