1996 Fiscal Year Final Research Report Summary
Various inflammatory cytokines and cardiovascular cells
| Project/Area Number |
06670741
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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 | Jichi Medical School |
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Principal Investigator |
OKAWA Fujio Jichi Medical School, Lecture, 医学部, 講師 (90260827)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Uichi Jichi Medical School, Assistant Professor, 医学部, 助教授 (30221063)
KUSANO Eiji Jichi Medical School, Assistant Professor, 医学部, 助教授 (50102249)
SHIMADA Kazuyuki Jichi Medical School, Professor, 医学部, 教授 (90145128)
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| Project Period (FY) |
1994 – 1996
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| Keywords | Cytokine / IL-1b / IL-6 / Nitric oxide / Eicosanoid / Leukotriene D4 |
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| Research Abstract |
It is well recognized that inflammatory cytokines might be involved in the pathogenesis of various cardiovascular diseases. However, the molecular signaling mechanisms remain to be determined.
We investigated the effects of various inflammatory cytokines on the contractility of rat aorta and its molecular mechanism in cultured cardiovascular cells.
1. IL-6, not IL-2 or IL-8, is a potent inhibitor of vascular contraction, which effect is mediated through the increased cAMP synthesis. Its action is endothelium independent and mediated by the increased synthesis of prostacyclin rather than nitric oxide (NO) generation in cultured vascular smooth muscle cells (VSMC). On the other hand, IL-1b modifies its contraction by inducing gene expression of inducible nitric oxide synthase (iNOS), thereby leading to generation of NO via tyrosine kinasedependent mechanisms and this IL-b action could be also modulated by TGF-b at iNOS mRNA levels.
2. IL-1b responsive iNOS,which is an important regulator of contractile function of the heart, is present in cardiac myocytes but not in cardiac fibroblasts. Besides, cAMP upregulates IL-1b-induced iNOS expression in cardiac myocytes.
3. IL-1b induces the accumulation of eicosanoid metabolites as well as NO in VSMCs. Cyclooxygenase pathway metabolites negatively modulate IL-1b induced NO production, while the 5-lipoxygenase metabolites, such as leukotriene D4, stimulate the NO production, both at posttranscriptional levels.
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