A review of Proteases and Antiproteases for Immune Regulation and Potential Therapeutic Application in Pulmonary Fibrosis.

Interstitial lung diseases (ILDs), or diffuse parenchymal lung diseases, are general terms for a group of over 200 conditions that result from the destruction of cells neighbouring the alveoli, leading to extensive inflammation and fibrosis of the lungs. Although different types of ILD have distinct pathophysiology, clinical display and advancement, many forms drive irreversible pulmonary fibrosis (PF), leading to progressive functional impairment, respiratory failure, and mortality. Key components of innate immunity include proteases and their cognate inhibitors, which are involved in respiratory homeostasis. Alterations to the protease-antiprotease balance can lead to pulmonary disease and fibrotic scarring of the lungs, and over the past two decades, there has been a surge in research exploring their effect on the pathogenesis of ILDs. We have evaluated relevant studies regarding these enzymes in the context of lung fibrosis and have discussed prospects for developing novel treatments. This review will place greater emphasis on the overall effect of proteases and antiproteases to the development of PF as studied using both in vivo and in vitro models. Considering the limited therapeutic interventions, continued research on proteolytic enzymes and their inhibitors is required for the development of novel, effective treatments for PF.