All animals were relatively recovered by 24 h. Intratracheal instillation of NH<sub>3</sub> (1%) caused early symptoms of ALI including airway hyperresponsiveness, neutrophilic lung inflammation and altered levels of coagulation factors (increased fibrinogen and PAI-1) and early biomarkers of ALI (IL-18, MMP-9, TGFβ) which was followed by increased deposition of newly produced collagen 14 days later.
Our study reveals that p53-mediated induction of PAI-1 expression due to chronic CS exposure exacerbates lung inflammation through elaboration of CXCL1, CXCL2, and CXCR2.
The results indicate that PAI-1 is a critical mediator that controls the development of the early lung inflammation that is required for the activation of the later innate immune response necessary for the eradication of P aeruginosa from the distal airspaces of the lung.
The 4G allele of the 4G/5G polymorphism of the PAI-1 gene is associated with higher PAI-1 levels and an increased incidence of hospitalizations for pneumonia.
Finally, the PAI-1 mutants were more effective in reducing the neutrophil elastase and cathepsin G activities in an in vivo model of lung inflammation than were their physiological inhibitors.
Induction of PAI-1 by exposure of lung epithelial cells to uPA is a newly recognized pathway by which PAI-1 could regulate local fibrinolysis and urokinase-dependent cellular responses in the setting of lung inflammation or neoplasia.