| Project/Area Number |
13670727
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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 |
Circulatory organs internal medicine
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| Research Institution | Kumamoto University |
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Principal Investigator |
OGAWA Hisao School of Medicine, Professor, 医学部, 教授 (50177135)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Coronary spastic angina / Unstable angina / Flow cytometer / Interferon-gamma / Interleukin-4 / Intracellular cytokine / Th1 cell / Th2 cell / T helper cell / interleukin-18 / CD40 ligand / interferon-γ |
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| Research Abstract |
Patients with unstable angina (UA) show increased frequencies of lymphocyte and monocyte activation in the peripheral blood. Coronary artery spasm plays an important role in the pathogenesis of ischemic heart diseases such as UA and acute myocardial infarction. Nitric oxide plays an important role in coronary artery spasm. We previously reported a deficiency in the nitric oxide activity in the spasm arteries of patients with coronary spastic angina (CSA). Others have reported that nitric oxide influences the immune response. Therefore, we investigated the balance between Th1-type and Th2-type responses in patients with CSA by evaluating the frequencies of interferon (IFN)-gamma-producing T cells and interleukin (IL)-4-producing T cells in the peripheral blood of such patients.
Peripheral blood mononuclear cells were collected from 50 consecutive patients with CSA, 23 consecutive patients with UA, 36 patients with stable angina, and 21 patients with chest pain syndrome. Cytokine-producing CD4+ T cells were quantified by 3-color flow cytometry after stimulation with phorbol myristate acetate and ionomycin. UA and CSA were associated with a significant increase in the frequency of CD4+ T cells producing IFN-gamma, whereas these conditions caused no significant difference in the frequency of CD4+ T cells producing IL-4. Recently, the potential for nitric oxide to act as an immunoregulator altering Th1/Th2 cytokine production has been demonstrated. Therefore, we investigated the effect of nitric oxide on cytokine production in CD4+ T cells. Culturing with a nitric oxide donor compound for 24 hours before stimulation, inhibited the increase in the frequency of CD4+ T cells producing IFN-gamma.
We demonstrated that there was a preference towards the Th1-type response in patients with CSA and that T cells showed a reduced Th1-type response after treating them with NO.
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