NEUTROPHIL ELASTASE INCREASES SECRETORY LEUKOCYTE PROTEASE INHIBITOR TRANSCRIPT LEVELS IN AIRWAY EPITHELIAL-CELLS

Airway inflammation is often associated with the infiltration of activ ated neutrophils and subsequent protease release. Although aiding in t he digestion and phagocytosis of foreign proteins and microorganisms, neutrophil proteases can indiscriminately damage healthy lung tissue. In the conducting airway, proteases, particularly neutrophil elastase, are counterbalanced by several antiproteases, including secretory leu kocyte protease inhibitor (SLPI). SLPI can be produced locally by a nu mber of cells including the airway epithelial cell. To examine the eff ects of neutrophil granule components on SLPI transcript levels, airwa y epithelial cells were treated (up to 96 h) with elastase, other prot eases, or enzymes isolated from human sputum. We found that neutrophil elastase increased SLPI transcript levels in primary and transformed human airway epithelial cells in a time- and dose-dependent manner. Ot her neutrophil products, such as cathepsin G, myeloperoxidase, and lys ozyme, had little or no effect on SLPI transcript levels. However, two nonneutrophil proteases, trypsin and pancreatic elastase, also increa sed SLPI transcript levels at higher doses than that required of neutr ophil elastase. Two inflammatory cytokines, tumor necrosis factor-alph a and interleukin-8, produced little or no effect on SLPI transcript l evels. This study demonstrates one way in which SLPI is regulated, via a protease that it inhibits, neutrophil elastase.