| Project/Area Number |
16590713
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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 | KITASATO UNIVERSITY |
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Principal Investigator |
IZUMI Tohru Kitasato University, School of Medicine, Professor, 医学部, 教授 (80143775)
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| Co-Investigator(Kenkyū-buntansha) |
INOMATA Takayuki Kitasato University, School of Medicine, Assistant Professor, 医学部, 講師 (20311954)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | DILATED CARDIOMYOPATHY / AUTOIMMUNE / Gi PROTEIN SIGNAL / ERYTHROPOIETIN / T CELL / G蛋白シグナル阻害 / β遮断薬 |
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| Research Abstract |
The G protein through β-adrenergic receptors has been focused on as a modulator of not only myocardial contractility but also immune response. Thus, firstly, the immunomodulatory effects of the inhibitory G (Gi) protein on myocardial inflammation are studied. Myosin-immunized Lewis rats (EAM : experimental autoimmune myocarditis/cardiomyopathy) were divided into two groups : administered with pertussis toxin (PTX), a representative Gi protein inhibitor, simultaneously with immunization (in induction phase) and the other administered after immunization (in effector phase). They were evaluated adjunctive effect of PTX on EAM. With the use in induction phase, PTX deteriorated EAM. On the other hand, in the use in effector phase, PTX improved its disease severity. This bidirectional G protein signal must be one of the major immunomodulating pathways in autoimmune cardiomyopathy.
On the other hand, erythropoietin (EPO) has a protective effect on myocardial damage. Thus, secondly, immunomodulatory effects of EPO on myocardial inflammation were investigated. EAM rats were treated daily with either EPO. EPO markedly reduced severity in EAM with the reduction of IFN-gamma/troponin T and IL-10/TNTmRNA in the myocardium. Although EPO did not suppress the proliferation of myosin-specific, myocarditogenic T cells in vitro, EAM produced by intravenous transfer of those T cells were ameliorated by daily administration of EPO. EPO has anti-inflammatory effect on the effecter phase.
For establishment of new method to make a diagnosis of autoimmune myocarditis in human being, the above mentioned two points are taken into account : Gi protein signal as beta-stimulation and erythropoietin as an intrinsic humoral factor.
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