Curcumin alleviates IL-17A-mediated p53-PAI-1 expression in bleomycin-induced alveolar basal epithelial cells.

Bleomycin-mediated inflammatory pathway is known to play an important role in the up regulation of oxidative stress. IL-17A is a pro-inflammatory cytokine involved in the modulation of fibrosis. The complex underlying mechanism for the said phenomenon remains unclear. This newly defined investigation was designed to understand the changes associated with 1L-17A mediated up-regulation of p53 and PAI-1 expression and the role of curcumin in attenuating this process. A549 cells were treated with bleomycin (BLM) and IL-17A to induce the inflammatory response in vitro. Curcumin, a known anti-inflammatory bioactive compound was administered as an intervention. Cytotoxicity in the treatment groups was assessed using Methyl thiazolyl tetrazolium (MTT) assay. Cell migration was evaluated using scratch assay. Protein expressions were studied using Western blot analysis for the downstream effector molecules of IL-17A mediated inflammatory pathways. In MTT assay, BLM treatment showed cytotoxicty upto 88% at a concentration of 1000 μM after 48 h of treatment. Cell migration assay results revealed that curcumin blocked the migration of cells to the area of the scratch. BLM treatment to the cells significantly induced the expression of pro-inflammatory cytokine IL-17A, which in turn modulated p53-PAI-1 expression. Bioactive compound curcumin showed anti-inflammatory and anti-apoptotic activity. Curcumin also regulated the BLM and IL-17A mediated changes in p53-PAI-1 expression. Curcumin has the ability to regulate inflammatory cytokines during BLM-induced injury and their effect on p53-PAI-1 expression. It can be used as a potential anti-inflammatory and anti-fibrinolytic component for intervening the epithelial cell damage.Very little information is provided till date on the inflammatory mechanism controlling the fibrinolytic system in acute lung injury (ALI). Damage to alveolar epithelial cells during ALI is important in the development of pulmonary fibrosis (PF). Most forms of ALI are characterized by defective alveolar fibrinolysis, inflammation, and fibrotic lesions. Recent reports show that alveolar epithelial cells express uPA, uPAR, and p53-mediated changes inhibit epithelial cell viability contributing to ALI. Thus, the roles of pulmonary epithelial cells in the inflammatory cascades activated after noninfectious injury, and the key signaling mediators of this process were actively investigated in this study. This investigation revealed that curcumin is an effective inhibitor of BLM-induced inflammation, apoptosis, and migration of basal alveolar epithelial cells. These results throw an insight into the possibility of developing curcumin as a novel therapeutic for ALI.