| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
The carbon tetrachloride-induced hepatic injury model has been used for investigating hepatitis mechanisms or for screening anti-hepatitis drugs. We have recently found that IL-6 is induced in plasma of rats by s.c. or i.p. injection of carbon tetrachloride, but not by its p.o. ingestion, and suggested that IL-6 suppresses the development of liver injury.
First, the site of IL-6 production was examined Since IL-6 was detected in peritoneal exudates fluid more than in plasma after i.p. carbon tetrachloride administration, the site of IL-6 production was expected to be done in some tissues or cells in the peritoneal cavity. IL-6 mRNA was observed to be expressed more in the peritoneum, omentum, and diaphragm in the carbon tetrachloride treated rats than control. However, there was no difference in IL-6 mRNA expression of liver, spleen, and kidney between the experimental and control animals. These results suggest that IL-6 mRNA is expressed in the serosal membrane in the peritoneal cavity, when rats are treated i.p. with carbon tetrachloride.
Next, inflammatory factors mediating IL-6 production were examined In the peritoneal exudate fluid, PGE_2 and histamine were increased 30 min after, and IL-1α and TNFα were increased with a peak at 1 hr after i.p. CCl_4 administration. These four factors were assayed for IL-6-indudng activity in the culture of mesothelial cells, which were separated from the intraperitoneal serous membrane by incubating with trypsin-EDTA. PGE_2, IL-1α, and TNFα except histamine tested stimulated IL-6 production in a dose-dependent manner. These results suggest that carbon tetrachloride induces PGE_2, IL-1α or TNFα in peritoneal exudates, which may be derived from peritoneal cells, and then, these factors stimulate IL-6 production in the peritoneal serous membrane.
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