Research of Immune Response viaToll-like Receptors and Infection Control in Severe Acute Pancreatitis
| Project/Area Number |
18591515
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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 |
Digestive surgery
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| Research Institution | Kobe University |
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Principal Investigator |
SHINZEKI Makoto (2007) Kobe University, Hospital Surgery, Medical Staff (60444593)
上田 隆 (2006) 神戸大学, 医学部附属病院, 助手 (80346262)
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| Co-Investigator(Kenkyū-buntansha) |
KURODA Yoshikazu Kobe University, Graduate school of Medical Science, Surgeiy, Professor (70178143)
安田 武生 神戸大学, 医学部附属病院, 医員 (20403248)
新関 亮 神戸大学, 医学部附属病院, 医員 (60444593)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,130,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | severe acute pancreatitis / toll-like receptors(TLR) / HMGB1 / inflammation / immune response / organ dysfunction / infection / Toll受容体 |
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| Research Abstract |
1. Expression of toll-like receptors (TLR), immune response via TLR, and role of TLR in severe acute pancreatitis (SAP)
1) On alveolar macrophages from rats with SAP, expressions of TLR2 and TLR4 (mRNA and protein) were significantly decreased, and cytokine production was also significantly diminished.
2) In intestinal mucosa in rats with SAP, TLR2 and TLR4 were expressed at the top of villi and crypt (especially at Paneth cells). The expressions of TLR2 and TLR4 proteins and NFκB activation were increased in the early phase and decreased in the late phase.
3) The TLR4-deficient mice had significantly lower serum levels of AST, ALT, BUN, and creatinine; significantly lower serum levels of IL-1 and TNF; reduced apoptosis of the liver and kidney; and a significantly higher rate of positive gram-negative bacterial cultures of the pancreas.
2. Expression of HMGB1 and its significance in severe acute pancreatitis
1) Serum HMGB1 levels were significantly increased in patients with SAP and were correlated with disease severity.
2) Serum HMGB1 levels were significantly increased in experimental SAP and expression of HMGB1 was increased in major organs (pancreas, liver, kidney, lung, and small intestine) injured during SAP.
3) Blockade of HMGB1 by anti-HMGB1 antibody attenuated the development of SAP and associated organ dysfunction, but worsened the bacterial translocation to pancreas.
3. Blood levels of new mediators related to immune response in severe acute pancreatitis
1) Serum IL-15 levels were increased significantly in severe acute pancreatitis, and they were correlated with severity scores. Serum IL-15 levels were greater in patients with organ dysfunction, patients with infection, and nonsurvivors.
2) Serum LAP levels were elevated in patients with SAP but were significantly lower in patients with higher grade of severity or pancreatic necrosis.
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Report
(3 results)
Research Products
(46 results)
