| Project/Area Number |
11470481
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Tohoku University |
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Principal Investigator |
OHUCHI Kazuo Graduate School of Pharmaceutical Sciences, Tohoku University, Professor, 大学院・薬学研究科, 教授 (20006357)
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| Co-Investigator(Kenkyū-buntansha) |
HIRASAWA Noriyasu Graduate School of Pharmaceutical Sciences, Tohoku University, Associate Professor, 大学院・薬学研究科, 助教授 (80181155)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥10,500,000 (Direct Cost: ¥10,500,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2000: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥5,100,000 (Direct Cost: ¥5,100,000)
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| Keywords | p44 / 42 MAP kinase / p38 MAP kinase / Neutrophils / Eosinophils / Mast cells / Macrophages / Epithelial cells / Steroid anti-inflammatory drug / p38MAP kinase / STAT1 / アポトーシス / デキサメサゾン / p42 / 44 MAP kinase / ICAM-1 / ヒスタミン / 肥満細胞 / cyclooxygenase-2 / interleukin-4 / macrophage inflammatory protein-2 |
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| Research Abstract |
In the present study, roles of MAP kinases in various responses of inflammatory cells (neutrophils, eosinophils, macrophages, mast cells, epithelial cells) were analyzed. Our findings were as follows: (1) Stimulation of neutrophils with staurosporine induced the production of macrophage inflammatory protein-2 (MIP-2). Both p44/42 MAPK and p38 MAPK participate the stabilization of MIP-2 mRNA and translation of MIP-2 protein. (2) Interleukin-5-induced survival of eosinophils was independent on p44/42 MAPK. In contrast, the apoptosis of the neutrophils infiltrated in the inflammatory sites was mediated by the continuous activation of p38 MAPK. (3) Stimulation of macrophages with staurosporine increased the release of arachidonic acid. The increase in the release of arachidonic acid was due to the phosphorylation of cytosolic phospholipase A_2 by p44/42 MAPK. In addition, in RAW264.7 cells, thapsigargin induced the induction of histidine decarboxylase and histamine production. The transcription of histidine decarboxylase was also regulated by p44/42 MAPK. (4) In mast cells, p38 MAPK partially participated in the antigen-induced interleukin-4 production. (5) MAPKs did not mediate IFN-γ-induced ICAM-1 expression in epithelial cells. In addition, we demonstrated that steroid anti-inflammatory drugs inhibited arachidonic acid release and histamine production in macrophages via inhibiting the activation of MAPKs. MAPK inhibitors showed almost equal inhibitory effect on these responses with the steroid anti-inflammatory drug. These findings suggest that MAPK is one of the targets for development of a new anti-inflammatory drug.
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