| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Outline of Final Research Achievements |
This study investigated the role of protein S in acute alcoholic hepatitis. A mouse overexpressing human protein S (hPS-TG) was generated in which acute hepatitis was induced by intraperitoneal injection of ethanol. The levels of serum liver enzymes, liver tissue inflammatory cytokines and the degree of hepatic steatosis were significantly increased in hPS-TG mice treated with ethanol. Cell expansion, activation and inhibition of apoptosis were significantly augmented in natural killer T (NKT) cells from hPS-TG mice. In a co-culture system of hepatocytes and NKT cells, the effects of protein S on ethanol-mediated cell injury were suppressed by a CD1d neutralizing antibody. NKT cells from patients with alcoholic hepatitis had increased levels of protein S and CD1d mRNA. Protein S exacerbates acute alcoholic hepatitis by enhancing the activation of NKT cells, indicating that protein S may be a molecular target for therapy of this disease.
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