| Project/Area Number |
01570365
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | Nagoya City University |
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Principal Investigator |
MATSUMOTO Yoshifuji Nagoya City University Medical School, Division of Blood Transfusion Service, Associate Professor, 医学部, 助教授 (40080155)
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| Co-Investigator(Kenkyū-buntansha) |
HIBINO Noriyuki Nagoya City University Medical School, 2nd. Department of Internal Medicine, Ass, 医学部, 助手 (40228747)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1990: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1989: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Systemic Lupus Epythematosus (SLE) / Autonmmune Disease / Calmodulin / Protein Kinase C / Intracellular Signal Transduction / Immmunology / 細胞内情報伝達系 / ホルボ-ルエステル / インタロイキン2 / カルモデュリン阻害剤 |
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| Research Abstract |
We investigated the abnormality of intracellular signal transduction, especially in calmodulin (CaM) and protein kinase C (PKC) systems, in lymphocytes from patients with systemic lupus erythematosus (SLE). A potent inhibitor of CaM, W-7 (using W-5, as control chemicals of W-7), suppressed the mitogen (PHA or SAC) -induced proliferative responses of T and B cells from normal and lupus patients. However, those suppressive effects were not observed in active lupus. W-7 affected more prominently Con A-induced suppressor T cells from active lupus. Spontaneous IgM-production from unstimulated B cells was inhibited and suppressive IgM-production of mitogenーstimulated B cells from active lupus was recovered by W-7. After activation of PKC by TPA, lower PHA-responsiveness of T cells and Con A-induced suppressor T cells were recovered in SLE patients. The production of IL-2 from PHA-stimulated T cells in SLE was augmented by TPA. Spontaneous IgM-production from unstimulated B cells in active lupus was suppressed by TPA. A potent inhibitor of PKC, H-7 (using HA 1004, as control chemicals of H-7) suppressed completely the functions of T and B cells in lupus patients and normal individuals. Moreover, expression of IL-2 receptor and responsiveness of IL-2 were affected by TPA.
All these results suggested that abnormalities of intracellular signal transduction systems were dependent to impaired immunological functions of SLE.
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