| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1991: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1990: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Endothelin (ET), which is released from airway epithelial cells, elicits a potent bronchoconstriction, suggesting that ET plays an important role in regulating airway smooth muscle tone. Although airway epithelial cells can release ET, few study has been reported about the mechanism of ET release from epithelial cells. We, thus, studied the effect of chemical mediators on the synthesis of ET by cultured tracheal epithelial cells of the guineapig. Inflammatory mediators, such as histamine, prostaglandin F_<2*>, Platelet - activating factor (PAF), and bradyldnin had no effect on ET release, whereas prostaglandin E_2 and calcitonin gene related peptide (CGRP) stimulated the ET release from epithelial cells. Most cytokines including IL-1, IL-2, TNF, TGF-beta, upregulated the ET release and cordcosteroid downregulated one. These results lead us to the hypothesis that the release of ET from airway epithelial cells might increase under inflammation or immune response. Therefore, we are now investigating the effect of inflammatory cells on the ET synthesis by airway epithelial cells.
Previously, we reported the ET-induced airway smooth muscle relaxation after an an anaphylactic reaction in vitro. We determined the characteristics of this relaxation. The airway relaxation was elicited by ET-1 and ET-2, but not by ET-3. Epithelial removal increased and lipoxygenase inhibitors decreased this relaxation response. These results suggest that ET causes the airway smooth muscle relaxation via ET_A receptor and this response might be mediated by one of lipoxygenase products.
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