| Project/Area Number |
10670523
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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 |
Gastroenterology
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| Research Institution | University of Occupational and Environmental Health |
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Principal Investigator |
YAMADA Shinwa U.O.E.H., Health Sciences, Professor, 産業保健学部, 教授 (60143426)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | Transplantation / Fatty Liver / Ischemia-Reperfusion / Neutrophil / NF-κB / Chemokine / Apoptosis / Gender-Difference |
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| Research Abstract |
1) Long-term ethanol consumption enhances an ability to produce cytokine-induced neutrophil chemoattractant (CINC) in the rat liver : Rats were pair-fed a liquid diet containing ethanol or dextrose for 6-8 wk. They were given lipopolysaccharide (LPS) and chemokine mRNA expression in the liver was evaluated. CINC mRNA expressions in the liver after 2 and 6 hr were significantly higher in the ethanol-fed group than the control. Female alcoholic rats showed higher level of CINC mRNA in the liver than the male rats 2 hr after LPS injection. It was shown that gonadectomy totally abolished the gender difference in CINC mRNA of the liver. We conclude that CINC induction may be responsible for alcoholic hepatitis, and that the difference in ability to produce CINC is a factor contributory to the gender-difference of alcoholic liver disease.
2) Alcoholic fatty liver differentially induces CINC and hepatic necrosis after ischemia-reperfusion (I/R) : Next, we investigated a cascade of events from transcription factor activation to necrosis through cytokine-induction and apoptosis in fatty liver after I/R. Rats with alcoholic or non-alcoholic fatty liver were subjected to warm I/R and compared with control rats. Rats with alcoholic fatty liver developed severe hepatic necrosis after I/R, compared to rats with non-alcoholic fatty liver or control. Hepatic apoptosis increased in the 2 fatty liver models compared with the control. Alcoholic fatty liver showed a rapid increase in NF-κB binding activity at 1 hr after I/R, which preceded an increased expression of TNF-α and CINC. In contrast, non-alcoholic fatty liver showed neither NF-κB activation nor cytokine induction after I/R. Our results indicate that alcoholic fatty liver may differentially induce CINC production and hepatic necrosis after I/R. Furthermore, the present study suggests that apoptosis be responsible for the progression to hepatic necrosis when neutrophils are activated and recruited to the liver.
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