| Project/Area Number |
15591614
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | Hokkaido University |
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Principal Investigator |
MATSUDA Naoyuki Hokkaido Univ., Hokkaido Univ.Hosp., Inst., 大学病院, 助手 (50332466)
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| Co-Investigator(Kenkyū-buntansha) |
HATTORI Yuichi Hokkaido Univ., Grad.School of Med., Prof., 大学院・医学研究科, 助教授 (50156361)
GANDO Satoshi Hokkaido Univ., Grad.School of Med., Asso.Prof., 大学院・医学研究科, 教授 (30125306)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Toll-like receptor / sepsis / MyD88 / NF-kB / MODS / Toll-like receptor / sepsis / slide attack 理論 / TRAF6 / 遺伝子発現 |
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| Research Abstract |
Western blot analysis, northern blot analysis and immunehistochemistry revealed the expressions of many subtypes of toll-like receptors (TLRs) in major organs such as lung, heart, liver, kidney and spleen, and inflammatory cells such as a macrophage or neutrophile. Cell death tended to rise during sepsis, and apoptosis were easy to be caused in the many types of cells of major organs with much expression of TLRs. As a result, the expressions of TLRs were decreased as progression of sepsis by decreased function of the cells in major organs.
In this study process, it was found that activity of transcription factor nuclear factor-□B (NF-□B) depeneds on the expression of TLRs in lungs and TLR2 was upregulated by NF-kB activation via TLR4 intracelluer signaling. The severity of acute lung injury with sepsis was reduced by NF-kB decoy oligonucleotides to restrain TLR2 expression in the mouse lung. Moreover, upregulation of TLR4 in proximal tubule of a kidney was observed by activation of macrophage migration check factor (MIF) in septic mice. In addition, it was confirmed that MIF participated in increase of TLR4 expression in mouse lungs. These studies demonstrated that TLRs expressed in many major organs and their expression were regulated by small substances such as MIF in sepsis.
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