Premium
Interleukin 17A induces renal SGK1 expression in hypertension (1074.3)
Author(s) -
Norlander Allison,
Saleh Mohamed,
Harrison David,
Madhur Meena
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1074.3
Subject(s) - sgk1 , downregulation and upregulation , angiotensin ii , kidney , distal convoluted tubule , interleukin 23 , biology , microbiology and biotechnology , interleukin 17 , chemistry , endocrinology , cytokine , glucocorticoid , immunology , blood pressure , biochemistry , gene , nephron
We have previously shown that the pro‐inflammatory cytokine, interleukin 17A (IL17A), is upregulated by angiotensin II and plays a critical role in angiotensin II induced hypertension and vascular dysfunction. However, the mechanism by which IL17A promotes hypertension is not known. IL17A is produced by a subset of CD4+ T helper cells termed Th17 cells that also produce the related isoform, IL17F. We have preliminary data that only IL17A, not IL17F, promotes hypertension. Recently, it has been shown that serum and glucocorticoid kinase 1 (SGK1) in T cells induces the differentiation of naïve CD4+ T cells into IL17A‐producing Th17 cells in a salt‐dependent manner. We tested the hypothesis that IL17A could in turn upregulate renal SGK1 to induce salt and water retention in the kidney in a feed forward fashion. Using cultured human proximal tubule cells (HK‐2 cells), we found that IL17A, but not IL17F, upregulated SGK1 mRNA expression 4‐fold in a dose‐dependent manner. In vivo, angiotensin II infusion upregulated renal SGK1 expression in wild type C57 mice, and this effect was abolished in IL17A deficient mice. These studies are the first to describe a link between IL17A and the induction of renal SGK1 and thus provide a potential mechanism by which IL17A, but not IL17F, modulates salt and water retention and blood pressure.