INHIBITION OF INDUCIBLE NITRIC-OXIDE SYNTHASE EXPRESSION BY INTERLEUKIN-4 AND INTERLEUKIN-13 IN HUMAN LUNG EPITHELIAL-CELLS

Nitric oxide produced by the inducible enzyme, nitric oxide synthase ( iNOS), is implicated in immunological and inflammatory processes. We d etermined the effects of T-helper (Th)2-derived cytokines on the induc tion of iNOS from an epithelial A549 cell line and human airway epithe lial cells stimulated by a mixture of interleukin-1 beta (IL-1 beta), interferon-gamma (IFN-gamma) and tumour necrosis Factor-alpha (TNF-alp ha). Interleukin-4 (IL-4) and interleukin-13 (IL-13) but not interleuk in-10 (IL-10) inhibited both iNOS mRNA expression and nitrite release in A549 cells. On human airway epithelial cells, IL-4 and IL-13 reduce d iNOS mRNA expression. Dexamethasone also inhibited both iNOS express ion and nitrite release. Th2 cytokines, IL-4 and IL-13, inhibit iNOS u pregulation by Th1 cytokines, indicating an important reciprocal role of Th1 and Th2 T-cell subsets on lung epithelial cells.