Inhibition of NF-κB activation and augmentation of IκBβ by secretory leukocyte protease inhibitor during lung inflammation

In earlier experiments, exogenous administration of secretory leukocyte protease inhibitor (SLPI) suppressed acute lung injury induced by deposition of 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 extravascular leakage of I-125-albumin, the intensity of up-regulation of lung vascular intercellular adhesion molecule-1, and the numbers of neutrophils accumulating 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-activated 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 levels of lung I kappa B beta (but not I kappa B alpha) protein in the absence of elevated mRNA for I kappa B beta. When instilled into normal lung, SLPI also caused similar changes (increases) in lung I kappa B beta, Finally, in the lung inflammatory model used, the presence of anti-SLPI caused accentuated activation of MF-kappa B, These data confirm the anti-inflammatory effect 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 inflammation.