| Project/Area Number |
14571164
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Kansai Medical University |
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Principal Investigator |
SATO Masahito Kansai Medical University, Faculty of Medicine, Instructor, 医学部, 助手 (30278626)
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| Co-Investigator(Kenkyū-buntansha) |
HAMADA Yoshinori Kansai Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (00172982)
OKUMURA Tadayoshi Kansai Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (80113140)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Nitric oxide(NO) / epidermal growth factor(EGF) / Interleukin(IL)-1 receptor 1 / NF-κB / IL-1β |
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| Research Abstract |
Epidermal growth factor (EGF) is one of trophic factors for intestinal adaptation after small bowel transplantation (SBT). Recent report indicates that nitric oxide (NO) has cytoprotective effect on bacterial translocation (BT) after SBT. We hypothesized that EGF stimulates the expression of inducible nitric oxide synthase (iNOS) gene in the graft after SBT, followed by increased production of NO, resulting in the decrease of BT.
Intestinal epithelial cells (IEC-6) were treated with EGF or/and interleukin-1β (IL-1β) in the presence and absence of phosphatidylinositol 3-kinase (PI3K) and EGF receptor kinase inhibitors (LY294002 and tyrphostin A25). The induction of NO production and iNOS, and its signal molecules including the inhibitory protein of NF-κB (IκB), nuclear factor-κB (NF-κB) and Akt were analyzed.
IL-1β stimulated the degradation of IκB and the activation of NF-κB, but had no effect on iNOS induction. EGF, which had no effect on the NF-κB activation and iNos induction, stimulated the up-regulation of type 1 interleukin-1 receptor (IL-1R1) through PI3K/Akt. Simultaneous addition of EGF and IL-1b stimulated synergistically the induction of iNOS, leading to the increased production of NO.
Our results indicate that EGF and IL-1β stimulate two essential signals for iNOS induction in IEC-6 cells, the up-regulation of IL-1R1 through PI3K/Akt and the activation of NF-κb through IκB kinase, respectively. Simultaneous addition of EGF and IL-1β can enhance the production of NO, which may contribute to the cytoprotective effect of EGF against intestinal injury.
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