Role of Inflammatory Cytokines and Fibrinolytic System in Pulmonary Fibrosis and the Efficiency of Curcumin in Regulating Them

Abstract

Idiopathic pulmonary fibrosis (IPF) is a type of interstitial lung disease (ILD) characterized by progressive deterioration and the development of permanent tissue scarring. This scarring results from inflammation, ineffective tissue healing, and fibrosis. The interstitial space and alveolar septa contain an abundance of extracellular matrix (ECM) proteins, notably fibronectin and collagen, which significantly promote fibrosis. This study aimed to determine the involvement of inflammatory cytokines and the fibrinolytic system in the underlying mechanisms of idiopathic pulmonary fibrosis. The research also assessed the ability of curcumin to regulate different fibrotic molecules and pathways. newlineTo scientifically provide evidence for the proposed aim, a bleomycin (BLM) induced pulmonary fibrosis model was prepared in C57BL/6 mice and used intraperitoneal injection of curcumin (75 mg/kg) as an intervention. The current study screened the normal and altered expressions of inflammatory cytokines, proteins in the fibrinolytic system, and tissue remodeling proteins in the inflammatory phase, progressive fibrosis phase as well as in the established fibrosis phase of the pulmonary fibrosis model. It was observed that BLM exposure increased the expressions of inflammatory cytokines, IL-17A, IL-23, and TNF-and#945;, in the inflammatory phase of the pulmonary fibrosis model. However, curcumin could significantly reduce the expression of these inflammatory cytokines suggesting its potential anti-inflammatory role against inflammation-mediated pulmonary fibrosis. BLM exposure also altered the normal expression levels of proteins in the fibrinolytic system, uPA, uPAR, and PAI-1. Conversely, curcumin intervention could bring back the normal expression levels of these proteins in the inflammatory and progressive fibrosis phases of the fibrosis model. Another important observation made was the altered expression patterns and restoration of normal expression levels of tissue remodeling proteins, MMP-2 and MMP-9, in the BLM-exposed group and