Regulation of 15-lipoxygenase isozymes and mucin secretion by cytokines incultured normal human bronchial epithelial cells

Objective and Design: To study the effects of IL-4, IL-13, IL-1 beta, IL-8 and TNFalpha on 15-lipoxygenase(15-LO) isozyme expression and mucin secreti on in normal human bronchial epithelial cells. Material and Methods: The effects of IL-4, IL-13, IL-1 beta, IL-8 and TNFal pha on 15-LO isoenzyme mRNA and protein expression, total 15-LO enzyme acti vity and mucin secretion were examined in cultures of normal human bronchia l epithelial cells. In addition, in order to determine whether the observed effects on mucin secretion were due to lipoxygenase (LO) products, the eff ect of the non-selective LO inhibitor nordihydroguaiaretic acid was examine d. Results: IL-4 and IL-13 selectively enhanced 15-LOa mRNA and protein levels , and total 15-LO enzyme activity. In contrast, no changes were observed in 15-LOb mRNA or protein levels. IL-4 and IL-13 both reduced mucin secretion in this cell type, however the non-selective LO inhibitor nordihydroguaiar etic acid had no effect on this action of IL-4. Conclusions. These data demonstrate that IL-4 and IL-13 selectively regulat e the expression of the 15-LOa isozyme. However, 15LOa products do not medi ate the IL-4-induced reduction in mucin secretion observed in this cell typ e.