|Budget Amount *help
¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1999 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1998 : ¥1,900,000 (Direct Cost : ¥1,900,000)
There is increasing evidence that nitric oxide (NO) is synthesized and released in the airways, thereby playing a role in a variety of airway functions. In the present experiment, to determine whether epithelium-derived NO is involved in the regulation of Cl secretion and, hence, water secretion into the airway lumen, we studied isolated human bronchial epithelial cells in vitro. Patch clamp studies of isolated airway epithelium showed that intracellular adition of high calcium solution plus bradykinin, or the NO donors S-nitroacetyl-N-penicillamine and nitroprusside caused an increase in Cl-selective current and open probability of luminal Cl channel. This effect was accompanied by the corresponding increase in NO-selective electrical current, as measured by a polarography using an NO-selective electrode, and induction of the presence of constitutive NO synthase (cNOS)-like immunoreactivities. On the other hand, stimulation of the cells with endotoxin from E. coli, interleukin-1β, tumor necrosis factor-α, or interferon-γ each increased Cl conductance and single Cl channel current. This effect was likewise accompanied by the increase in NO concentration in the medium, but, based on Nothern analysis and immunocytochemistry, expressions of iNOS mRNA and iNOS protein were upregulated by these stimuli. Futhermore,these effects were dose-dependently inhibited by 14-membered macrolides and glucocorticosteroids. Therefore, macrolides and steroids may be therapeutic potential for the treatment of airway hypersecretion in the inflamed airways.