Curcumin Improves Silica Induced Lung Fibrosis by Targeting TLR4-NLRP3 Inflammasome and TGF-β Inhibition in Mice Model.

Silicosis, a progressive occupational lung disease, caused by inhalation of crystalline silica particles, leads to chronic inflammation and pulmonary fibrosis. Increasing evidence suggests that activation of the TLR4/NF-κB signaling pathway and NLRP3 inflammasome plays a crucial role in silica-induced lung injury. This study was undertaken to investigate protective effects of curcumin against silica-induced pulmonary inflammation and fibrosis where its efficacy was compared with dexamethasone. For inducing silicosis, mice experienced silica exposure for 35 days, followed by intranasal curcumin administration. The study evaluated inflammatory responses, macrophage polarization, fibrotic alterations, and the expression of key mediators, including TLR4, NF-κB, NLRP3, ASC, caspase-1, IL-1β, TNF-α, IL-6, IL-18, TGF-β, and FN-1. Curcumin significantly reduced inflammatory cytokine expression, suppressed NLRP3 inflammasome activation, and promoted macrophage polarization toward the anti-inflammatory M2 phenotype. In addition, curcumin attenuated fibrosis by decreasing TGF-β and FN-1 expression, collagen deposition, and extracellular matrix accumulation. Histopathological findings confirmed reduced alveolar damage, silicotic nodules, goblet cell hyperplasia, mucus hypersecretion, and pulmonary fibrosis in curcumin treatment groups. This study established alleviation of silica-induced pulmonary inflammation and fibrosis by inhibiting TLR4/NF-κB and TGF-β signaling, suppressing NLRP3 inflammasome activation. It highlights the potential clinical significance of curcumin as a promising therapeutic agent in the management of silicosis and progressive lung fibrosis.