2000 Fiscal Year Final Research Report Summary
Research on transcription of mRNA of inducible NO synthase and supression of its degradation by proinflammatory cytokine.
| Project/Area Number |
11672172
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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 |
Biological pharmacy
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| Research Institution | University of Tokushima |
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Principal Investigator |
HISAYAMA Tetsuhro Univ. of Tokushima, Fac. Pharmaceut. Sci., Associate Professor, 薬学部, 助教授 (70130383)
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| Co-Investigator(Kenkyū-buntansha) |
HORIO Shuhei Univ. of Tokushima, Fac. Pharmaceut. Sci., Assistent Professor, 薬学部, 助手 (80145010)
FUKUI Hiroyuki Univ. of Tokushima, Fac. Pharmaceut. Sci., Professor, 薬学部, 教授 (90112052)
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| Project Period (FY) |
1999 – 2000
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| Keywords | vascular smooth muscle / TRAF6 / enzyme induction / proinflammatory cytokine / interleukin 1 / messenger RNA stability / p38 MAPkinase / inducible NO synthase |
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| Research Abstract |
In this research, we have carried out molecular cloning of TRAF6 involved in interleukin 1 (IL-1)-mediated expression of inducible nitric oxide synthase (iNOS), construction of its gene transfer system, and investigation on mechanisms of suppression of iNOS mRNA degradation via activation of IL-1 receptors. The transient expression of TRAF6 resulted in enhancement of the IL-1-induced iNOS mRNA production, while inhibited nuclear translocation of NF-kB by IL-1, suggesting a possibility that NF-kB could not necessarily mediate the IL-1-induced expression of the iNOS gene. Further, we for the first time, found that IL-1 suppressed a degradation of iNOS mRNA, and that p38 MAPkinase is involved in its signal transduction pathway. IL-1 selectively induced a double-phosphorylation of p38, but not on ERK or JNK, other subfamily of MAPkinases, and expression of a specific activator of p38, namely a constitutively activated variant of MKK6, suppressed a degradation of iNOS mRNA without application of IL-1. These results open a clue for development of new drugs and remedies against inflammatory diseases, and contribute to understanding of pathophysiological basis of proinflammatory cytokines.
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