Salt suppresses IFNγ inducible chemokines through the IFNγ-JAK1-STAT1 signaling pathway in proximal tubular cells

Yohei Arai, Daiei Takahashi, Kenichi Asano, Masato Tanaka, Mayumi Oda, Shigeru Ko, Minoru Ko, Shintaro Mandai, Naohiro Nomura, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara

Research output: Contribution to journalArticle

Abstract

The mechanisms of immunoactivation by salt are now becoming clearer. However, those of immunosuppression remain unknown. Since clinical evidence indicates that salt protects proximal tubules from injury, we investigated mechanisms responsible from salt causing immunosuppression in proximal tubules. We focused on cytokine-related gene expression profiles in kidneys of mice fed a high salt diet using microarray analysis and found that both an interferon gamma (IFNγ) inducible chemokine, chemokine (C-X-C motif) ligand 9 (CXCL9), and receptor, CXCR3, were suppressed. We further revealed that a high salt concentration suppressed IFNγ inducible chemokines in HK2 proximal tubular cells. Finally, we demonstrated that a high salt concentration decreased IFNGR1 expression in the basolateral membrane of HK2 cells, leading to decreased phosphorylation of activation sites of Janus kinase 1 (JAK1) and Signal Transducers and Activator of Transcription 1 (STAT1), activators of chemokines. JAK inhibitor canceled the effect of a high salt concentration on STAT1 and chemokines, indicating that the JAK1-STAT1 signaling pathway is essential from this mechanism. In conclusion, a high salt concentration suppresses IFNγ-JAK1-STAT1 signaling pathways and chemokine expressions in proximal tubules. This finding may explain how salt ameliorates proximal tubular injury and offer a new insight into the linkage between salt and immunity.

Original languageEnglish
Article number46580
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 2017 Jan 1

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Janus Kinase 1
C Chemokines
STAT1 Transcription Factor
Interferon-gamma
Salts
Chemokines
Immunosuppression
CXCR3 Receptors
CXC Chemokines
Wounds and Injuries
Microarray Analysis
Transcriptome
Immunity

ASJC Scopus subject areas

  • General

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Salt suppresses IFNγ inducible chemokines through the IFNγ-JAK1-STAT1 signaling pathway in proximal tubular cells. / Arai, Yohei; Takahashi, Daiei; Asano, Kenichi; Tanaka, Masato; Oda, Mayumi; Ko, Shigeru; Ko, Minoru; Mandai, Shintaro; Nomura, Naohiro; Rai, Tatemitsu; Uchida, Shinichi; Sohara, Eisei.

In: Scientific Reports, Vol. 7, 46580, 01.01.2017.

Research output: Contribution to journalArticle

Arai, Y, Takahashi, D, Asano, K, Tanaka, M, Oda, M, Ko, S, Ko, M, Mandai, S, Nomura, N, Rai, T, Uchida, S & Sohara, E 2017, 'Salt suppresses IFNγ inducible chemokines through the IFNγ-JAK1-STAT1 signaling pathway in proximal tubular cells', Scientific Reports, vol. 7, 46580. https://doi.org/10.1038/srep46580
Arai, Yohei ; Takahashi, Daiei ; Asano, Kenichi ; Tanaka, Masato ; Oda, Mayumi ; Ko, Shigeru ; Ko, Minoru ; Mandai, Shintaro ; Nomura, Naohiro ; Rai, Tatemitsu ; Uchida, Shinichi ; Sohara, Eisei. / Salt suppresses IFNγ inducible chemokines through the IFNγ-JAK1-STAT1 signaling pathway in proximal tubular cells. In: Scientific Reports. 2017 ; Vol. 7.
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abstract = "The mechanisms of immunoactivation by salt are now becoming clearer. However, those of immunosuppression remain unknown. Since clinical evidence indicates that salt protects proximal tubules from injury, we investigated mechanisms responsible from salt causing immunosuppression in proximal tubules. We focused on cytokine-related gene expression profiles in kidneys of mice fed a high salt diet using microarray analysis and found that both an interferon gamma (IFNγ) inducible chemokine, chemokine (C-X-C motif) ligand 9 (CXCL9), and receptor, CXCR3, were suppressed. We further revealed that a high salt concentration suppressed IFNγ inducible chemokines in HK2 proximal tubular cells. Finally, we demonstrated that a high salt concentration decreased IFNGR1 expression in the basolateral membrane of HK2 cells, leading to decreased phosphorylation of activation sites of Janus kinase 1 (JAK1) and Signal Transducers and Activator of Transcription 1 (STAT1), activators of chemokines. JAK inhibitor canceled the effect of a high salt concentration on STAT1 and chemokines, indicating that the JAK1-STAT1 signaling pathway is essential from this mechanism. In conclusion, a high salt concentration suppresses IFNγ-JAK1-STAT1 signaling pathways and chemokine expressions in proximal tubules. This finding may explain how salt ameliorates proximal tubular injury and offer a new insight into the linkage between salt and immunity.",
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