Cl ion transport and CFTR gene expression in antigen sensitized airway epithelium

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1. Antigen challenge increases C1 ion transport in sensitized guinea pig tracheaAntigen challenge causes hypersecretion in asthma. Allthough various mediators involved in asthma stimulate C1 ion transport, the direct effect of antigen challenge on C1 ion transport remains unclear. The short circuit current (Isc) in the presence of amiloride was measured in Ussing chamber in sensitized guinea pig tracheas. Ovalbumin (OA)-challenge induced monophasic increase in Isc. Pretreatment of the trachea with pyrilamine, but not cimetidine significantly inhibited OA-challenge induced increase in Isc (△Isc) in a dosedependent manner. Pretreatment with FK224 or sodium cromogycate also inhibited OA-induced △Isc. These data suggest that activation of sensitized mast cells by antigen challenge releases histamine, which increases C1 ion transport through direct epithelial action and via sensory C-fibers.2. Repeated antigen sensitization induces epithelial remodeling and elevation of C1 transport by CFTR upregulation in guinea pig trachea ; the role of IL-4To elucidate the mechanism of hypersecretion in chronic remodeled asthmatic airway, guinea pigs were injected with OA weekly four weeks, and assessed on the 6th week. Goblet cell hyperplasia, Isc in the presence of amiloride in Ussing chamber and CTFR-positive epithelial cells were significantly increased in sensitized trachea as compared with the control animals. These changes were inhibited by dexamethasone, Th2 inhibitor, or anti IL-4 antibody. We concluded that 1) repeated antigen sensitization and challenges induce goblet cell hyperplasia and elevation of Cl ion transport by upregulated CFTR expression, 2) Th2 cytokines, especially IL-4 may be involved in these mechanisms, 3) steroid and Th2 inhibitor may be useful for the treatment of hypersecretion in chronic asthma.