| Project/Area Number |
09670614
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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 |
Respiratory organ internal medicine
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| Research Institution | Tokushima University |
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Principal Investigator |
OGUSHI Fumitaka Tokushima University School of Medicine, Third Department of Internal Medicine, Associate Professor, 医学部, 助教授 (80201375)
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| Co-Investigator(Kenkyū-buntansha) |
YANAGAWA Hiroaki Tokushima University School of Medicine, Third Department of Internal Medicine, Associate Professor, 医学部・附属病院, 助手 (50263827)
NAKAMURA Yoichi Tokushima University School of Medicine, Third Department of Internal Medicine, Lecturer, 医学部・附属病院, 講師 (00237447)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | prostaglandin E2 / cyclooxygenase-2 / Th2 cell associated cytokine / 15-lipoxygenase / inflammatory cytokine synthesis inhibitor / シクロオキシゲナーゼ2 / 線維化 / PGE2 / Th2様サイトカイン / cyclooxygenase-2 / Th1様サイトカイン / サイトカイン産生抑制薬 / 線維芽細胞 / cyclooxygenase(COX)1 / COX2 / 単球・マクロファージ |
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| Research Abstract |
Pulmonary fibrosis is characterized by the proliferation of fibroblasts and collagen deposition. It is known that fibroblasts proliferation is regulated by the various factors. Prostaglandin (PG)E2, which is important mediator and is generated by various respiratory cells, such as alveolar macrophages (AM), fibroblasts and epithelial cells, has shown to inhibit fibroblasts proliferation and production of extracellular matrix protein. For this, PGE2 thought to play an important role on fibrotic process of lung. On the other hand, PGE2 production is thought to be regulated by Th 1, and Th2 cytokines. Th2 cytokines, such as IL-4, IL-10, IL-13, inhibited PGE2 production and COX-2 production in monocytes, whereas only IL-4 significantly suppressed them in AM. IL-4 up-regulated 15-lipoxygenase mRNA induction. Th1 cytokine, such as IFN-g, did not affect the PGE2 production from monocytes and AM. These results suggest that Th2 cytokine may attenuate the inflammation in the process of pulmonary fibrosis. Recently, cytokine biosynthesis inhibitors have been developed. We investigated the effect of FR167653(FR), which was one of cytokine biosynthesis inhibitors on PGE2 production and COX-2 induction. FR suppressed the PGE2 production and COX-2 induction. These results show that FR may be therapeutically useful for inhibiting production of both inflammatory cytokines and PG production in inflammatory diseases. Next, we examined the functional changes of lung fibroblasts in bleomycin(BLM)-induced rat pulmonary fibrosis. The growth of fibroblasts from BLM-lung(BLM-fibroblast) was more rapid than that of normal. Moreover, PGE2 synthesis of BLM-fibroblasts was less than that of control. Thus the decreased PGE2 production observed in BLM-fibroblasts may result in the excess fibroblast proliferation disorder.
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