2007 Fiscal Year Final Research Report Summary
Regulation of organ dysfunction and infectious complications after liver transplantation : in the view of innate immunity and the Kupffer cells
| Project/Area Number |
18591500
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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 | Chiba University |
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Principal Investigator |
TAKEUCHI Dan Chiba University, Universty Hospital, Assistant Professor (20400822)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Masaru Chiba University, Graduate School of Medicine, Professor (70166156)
YOSHIDOME Hiroyuki Chiba University, Graduate School of Medicine, Associate Professor (10312935)
OHTSUKA Masayuki Chiba University, Graduate School of Medicine, Assistant Professor (90334185)
KATO Atsushi Chiba University, University Hospital, Assistant Professor (70344984)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Transplantation / Regenerative Medicine / Immunology / Infection / Shear Stress / Cell Culture |
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| Research Abstract |
After 30 mins of portal vein ischemia, rats underwent 70% or 90% of hepatectomy followed by reperfusion. These rats were divided to 2 groups and one group underwent splenic artery (SPA) ligation, resulting in four groups. Significant activation of STAT 3 was noted in the remnant liver of rats with 70% hepatectomy and SPA ligation group. Also, significant activation of NFκB was observed in the same group. Immunohistochemistry revealed decreased expression of MRP-2 in the remnant liver of rats with 90% hepatectomy group compared with 70% hepatectomy group.
Cells in the sinusoidal space were isolated from the liver of hepatectomized rats. It was unable to obtain sufficient number of cells from the rats with 90% hepatectomy, due to the small amount of remnant liver. Adequate number of cells was obtained by putting cells from 3 rats together. Hepatic stellate cells (HSCs) from rats with 90% hepatectomy produced significantly higher amount of TGF-β compared with HSCs from rats with 70% hepate
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ctomy. Multiplication of hepatocytes from normal mice was suppressed when these cells were co-cultured with Kupffer cells from rats with 90% hepatectomy under stimulation with HGF, compared to hepatocytes cultured with Kupffer cells from rats with 70% hepatectomy. This effect was observed when cultured hepatocytes and Kupffer cells were allowed cell to cell contact.
To investigate antimicrobial peptide production, mice underwent 70% hepatectomy with or without administration of dexamethasone ip. No significant difference was observed in pulmonary expression of murine beta defensin (MBD) -1, 3 mRNA between two groups when there was no bacterial infection. Pulmonary defensin mRNA expression was attenuated in mice with hepatectomy and dexamethasone administration when mice were infected with Pseudomonas aeruginosa intratracheally. Gene transfer of MBD-1 into 293 cells was successful and protein expression was confirmed by western blot analysis. These cells were more resistant Pseudomonas aeruginosa than wild type when TCID_<50> of each cell group was determined. Less
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Research Products
(8 results)
