| Project/Area Number |
13470144
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | NARA MEDICAL UNIVERSITY (2002)
Kyoto University (2001) |
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Principal Investigator |
SAITO Yoshihiko Nara Medical University, First Department of Internal Medicine, Professor, 医学部, 教授 (30250260)
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| Co-Investigator(Kenkyū-buntansha) |
小川 佳宏 京都大学, 医学研究科, 助手 (70291424)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2002: ¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 2001: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | SOCS1 / SOCS3 / Cytokine Resistance / CT-1 / NF-_kB / SOCSI / サイトカイン / SOCS / カルディオトロピン / STAT / LPS |
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| Research Abstract |
CIS (cytokine inducible SH2 protein), SOCS (suppressor of cytokine signaling) or SSI (STAT-induced STAT inhibitor) proteins are a family of cytokine-inducible negative regulators of cytokine signaling via Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathways. Given the evidence that JAK-STAT pathway plays a critical role in the cardiovascular system, the primary objective of this study is to assess the effects of CIS family on JAK-STAT signaling in the cardiovascular system in rats treated with cardiotrophin-1 (CT-1), an interleukin-6 family of cytokine. Intravenous injection of 20μg/kg body wt of CT- 1 induced transient, markedly increase in STAT3 activation in various tissues including heart and lung, and subsequent up-regulation of two members of CIS family, JAK binding protein (JAB)/SOCS-1/SSI-1 and CIS3/SOCS-3/SSI-3 in same tissues. Pretreatment with the same dose of CT-1 60 minutes before significantly attenuated the STAT3 activation induced by a second injection of CT-1. In rats pretreated with CT-1 either the induction of iNOS mRNA or hypotension by subsequent CT-1 injection was not observed. Furthermore, we demonstrate that pretreatment with CT-1 attenuated left ventricular function induced by non-fatal dose of LPS and LPS-induced cardiac dysfunction was blunted in mice over-expressing JAB/SOCS-1 specifically in heart.
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