REGULATION OF SECRETORY LEUKOCYTE PROTEINASE-INHIBITOR (SLPI) AND ELASTASE-SPECIFIC INHIBITOR (ESI ELAFIN) IN HUMAN AIRWAY EPITHELIAL-CELLSBY CYTOKINES AND NEUTROPHILIC ENZYMES/

The regulation of the activity of potentially harmful proteinases secr eted by neutrophils during inflammation is important for the preventio n of excessive tissue injury. Secretory leukocyte proteinase inhibitor (SLPI), also called antileukoprotease (ALP) or mucus proteinase inhib itor (MPI), is a serine proteinase inhibitor that has been found in a variety of mucous secretions and that is secreted by bronchial epithel ial cells. We recently reported the presence of SLPI and of an elastas e-specific inhibitor (ESI), also called elafin, in the supernatants of two cell lines, NCI-H322 and A549, which have features of Clara cells and type II alveolar cells, respectively. We showed in addition that epithelial cell lines produce the elastase-specific inhibitor as a 12 to 16 kD precursor of the elafin molecule (6 kD) called pre-elafin. In the present study, we show that NCI-H322 cells produced higher amount s of both inhibitors than A549 cells and that basal production of SLPI in both cell lines is higher than the production of elafin/pre-elafin . In addition, we show that interleukin-1 beta and tumor necrosis fact or induce significant SLPI expression and are major inducers of elafin /pre-elafin expression. Moreover, induction is greater in A549 cells t han in NCI-H322 cells. The implications of these findings for the peri pheral airways are twofold: (1) alveolar epithelial cells may respond to cytokines secreted during the onset of inflammation by increasing t heir antiprotease shield; (2) elafin/pre-elafin seems to be a true loc al ''acute phase reactant'' whereas SLPI, in comparison, may be less r esponsive to local inflammatory mediators.