Effect oft–Butylhydroperoxide on Chloride Secretion in Rat Tracheal Epithelia

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Abstract
Oxidative stress has been known to play important roles in various inflammatory diseases of lung such as allergic bronchitis, dust particle–induced inflammatory diseases, or chronic bronchitis. However, the effects of oxidants on Cl secretion in tracheal epithelia have not been determined. To examine the effects of oxidants on Cl–secretion of the airway epithelia rat tracheal epithelial cells were cultured on porous filters and short circuit current (Isc) was measured in an Ussing chamber system.t–Butylhydroperoxide, which was widely used as a model substance to study the mechanism of cell injury resulted from oxidative stress, induced a transient increase in Iscby dose–dependent manner. The response was not observed in Cl––free medium, and inhibited by 100 μM bumetanide. N(–Diphenyl–l,4–phenylene–diamine (DPPD, 5 μM), an inhibitor of lipid peroxidation, blocked thet–butylhydroperoxide response. Whent–butylhydroperoxide was added after the administration of forskolin or H–89, a protein kinase A inhibitor, thet–butylhydroperoxide–induee Iscincrease was abolished. Pretreatment of indomethacin (10 μM) completely inhibited thet–butylhydroperoxide response, but pretreatment of thapsigargin (1 μM) did not. t–Butylhydroperoxide induced gradual increases in cytosolic Ca2+level, and increased [3H]arachidonic acid release in the presence of thapsigargin. These results indicate thatt–butylhydroperoxide stimulates Cl–secretion via activation of phospholipase A2and subsequent production of cyclooxygenase metabolites by Ca2+–dependent and –independent mechanisms.