Inhibition of NF-kappa B activation and augmentation of I kappa B beta by secretory leukocyte protease inhibitor during lung inflammation

In earlier experiments, exogenous administration of secretory leukocyte pro tease inhibitor (SLPI) suppressed acute lung injury induced by deposition o f IgG immune complexes. In the current studies we examined the mechanism of the protective effects of SLPI in this model. The presence of SLPI in the IgG immune complex-model of lung injury reduced the increase in extravascul ar leakage of I-125-albumin, the intensity of up-regulation of lung vascula r intercellular adhesion molecule-1, and the numbers of neutrophils accumul ating in the lung. The presence of SLPI caused greatly reduced activation ( ie, nuclear translocation) of the transcription nuclear factor-kappa B (NF- kappa B) in lung cells but did not suppress activation of lung mitogen-acti vated protein kinase. SLPI did not alter NF-kappa B activation in alveolar macrophages harvested 30 minutes after Initiation of lung inflammation. In the presence of SLPI, content of tumor necrosis factor-alpha,CXC chemokines , and C5a in bronchoalveolar fluids was unaffected. In the inflamed lungs, Inhibition of NF-kappa B activation by SLPI was associated with elevated le vels of lung I kappa B beta (but not I kappa B alpha) protein in the absenc e of elevated mRNA for I kappa B beta. When instilled into normal lung, SLP I also caused similar changes (increases) in lung I kappa B beta, Finally, in the lung inflammatory model used, the presence of anti-SLPI caused accen tuated activation of MF-kappa B, These data confirm the anti-inflammatory e ffect of SLPI in lung and point to a mechanism of anti-inflammatory effects of SLPI. SLPI appears to function as an endogenous regulator of lung infla mmation.