| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
Our series of experiments showed that cytotoxic T cells did not play a pivotal role in elimination of an intracellular pathogen, BCG.Therefore, we investigated the mechanism of genetic resistance to BCG, we have compared cytokine and nitric oxide synthase (NOS) responses of a genetically resistant mouse strain, B10, with those of a susceptible mouse strain, BALB/c. We have found that multiple steps of cytokine responses leading to induce NOS mRNA are impaired in BALB/c mice. The expressions of IL-12 and IFN-gamma mRNA in response to BCG infection appeared to be impaired in BALB/c mice as compared with B10 mice. In addition, our in vitro studies indicate that IFN-gamma-induced NOS mRNA expression of bone marrow macrophages is significantly low in BALB/c mice. Intriguingly, we recently found that IFN-gamma is able to induce IL-12 from macrophages (BBRC 198 : 557, 1994), suggestifng that potential positive regulatory circuit could be formed(IFN-gamma->macrophages ->IL-12 ->Th1 ->IFN-gamma). However, the response of IL-12 to IFN-gamma was also impaired in BALB/c mice. The impaired positive regulatory circuit, if exists in vivo, may substantially attenuate the production of NOS in BALB/c mice.
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