Abstract: SA-PO1055

A High Salt Diet Suppressed CXCL9 and CXCL10 in Proximal Tubules through the IFNγ-JAK1-STAT1 Signaling Pathway

Session Information

  • Na+, K+, Cl-
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Fluid, Electrolytes, and Acid-Base

  • 703 Na+, K+, Cl- Basic

Authors

  • Arai, Yohei, Graduate School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
  • Rai, Tatemitsu, Graduate School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
  • Uchida, Shinichi, Graduate School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
  • Sohara, Eisei, Graduate School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
  • Takahashi, Daiei, Graduate School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
  • Asano, Kenichi, School of Life Science, Tokyo University of Pharmacy and Life Sciences, Hachioji-shi, Tokyo, Japan
  • Tanaka, Masato, School of Life Science, Tokyo University of Pharmacy and Life Sciences, Hachioji-shi, Tokyo, Japan
  • Oda, Mayumi, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
  • Ko, Shigeru B.h., Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
  • Ko, Minoru S.h., Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
  • Mandai, Shintaro, Graduate School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
  • Nomura, Naohiro, Graduate School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
Background

The mechanisms of immunosuppression by salt remain unknown, despite the existence of many clinical evidences indicating that salt loading protects proximal tubules from injury. Therefore, we investigated the mechanisms of immunosuppression by salt in proximal tubules in vitro and in vivo.

Methods

We focused on cytokine-related gene expression profiles suppressed in kidneys of mice fed a high salt diet using microarray analysis and quantitative RT-PCR. We investigated the mechanism of these cytokine suppressions by salt using a cultured line of human proximal tubular epithelial cells (HK2) in vitro. Then, we confirmed this mechanism could apply equally to kidneys of mice fed a high salt diet in vivo.

Results

We found that IFNγ inducible chemokine ligands, CXCL9 and CXCL10, and a specific receptor, CXCR3, were suppressed in kidneys of mice fed a high salt diet using microarray analysis and quantitative RT-PCR. Then, we revealed that a high salt concentration suppressed these CXCLs induced by IFNγ in HK2 cells using ELISA. We demonstrated that a high salt concentration decreased IFNGR1 expression in the basolateral membrane of HK2 cells using biotinylation assay, leading to decreased phosphorylation of activation sites of JAK1 and STAT1, activators of CXCLs. JAK inhibitor canceled the effect of a high salt concentration on STAT1 and CXCLs, indicating that the JAK1-STAT1 signaling pathway is essential for this mechanism. Furthermore, we confirmed that the induction of CXCL9 and CXCL10 by IFNγ was suppressed in kidneys of mice fed a high salt diet using immunoblotting. Moreover, the phosphorylation of JAK1 was decreased in kidneys of mice fed a high salt diet.

Conclusion

A high salt diet suppresses the IFNγ-JAK1-STAT1 signaling pathway and the induction of chemokines in proximal tubules in vivo. This finding may explain how salt ameliorates certain kinds of proximal tubular injury and offer a new insight into the linkage between salt and immunity.

Funding

  • Government Support - Non-U.S.