| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
Pulmonary fibrosis is characterized by the proliferation of fibroblasts. It is known that fibroblasts proliferation is regulated by the various factors. Prostaglandin E2 (PGE2), which is important mediator and is generated by various respiratory cells such as alveolar macrophages, lung fibroblasts, and alveolar epithelial cells, has be shown to inhibit lung fibroblast proliferation and production of extracellular matrix proteins as collagen and fibronectin. For this, PGE2 thought to play an important role on the fibrotic process of lung. In this regard, mechanism of PGE2 production by fibroblast was investigated. IL-1beta stimulated fibroblast produced PGE2, depending on the IL-1-beta concentration. Cyclooxygenase (COX) activity of these cells was increased and was inhibited by NS-398, a cyclooxygenase specific inhibtor. As analyzed by Northern blot, COX-1 mRNA was detected with resting cells and did not increase by the addition of IL-1beta. In contrast, the COX-2 mRNA was indetectable with resting cells, but was increased dramatically by addition of IL-1. Th2 cell associated cytokine (IL-4) inhibited PGE2 production from fibroblasts, whereas Th1 cell associated cytokine (IFN-gamma) did not affect on PGE2 production. Then, we investigated the effect of IL-4, IL-10, and IL-13, products of the activated Th2 subset of CD4 T cells and IFN-gamma, a Th1 cell associated cytokine were examined on PGE2 production from LPS stimulated monocytes. PGE2 production and COX-2 synthesis in LPS-stimulated monocyte were increased in a dose dependent manner. Th2 cell associated cytokine inhibited COX2 synthesis resulting inhibtited PGE2 production, whreas Th1 cell associated cytokine did not affected. These results suggest that regulation of PGE2 production by Th1 and Th2 cell associated cytokine may be involved in the pathogenesis of pulmonary fibrosis.
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