INHIBITION OF NEUTROPHIL ELASTASE-INDUCED INTERLEUKIN-8 GENE-EXPRESSION BY URINARY TRYPSIN-INHIBITOR IN HUMAN BRONCHIAL EPITHELIAL-CELLS

Background: Urinary trypsin inhibitor (UTI), a potential inhibitor for proteinases including neutrophil elastase (NE), trypsin, plasmin, cat hepsin B and H, has been used for the treatment of lung diseases with the absence of side effects in Japan. Methods: In this study, we inves tigated the inhibitory effects of UTI on both purified NE and NE activ ities present in bronchoalveolar fluids from patients with chronic bro nchitis. We also investigated the inhibitory capacity of UTI with rega rd to NE-induced interleukin-X gene expression in human bronchial epit helial cells by Northern analyses. Results: UTI inhibited NE activitie s in bronchoalveolar lavage fluid from patients with chronic bronchiti s and of the purified enzyme. In addition, UTI inhibited NE-induced in terleukin-8 gene expression and protein secretion in a human bronchial epithelial cell line. Conclusions: Our results suggest that UTI is ap plicable to patients with a variety inflammatory lung diseases in whic h NE plays a pivotal role.