Curcumin Modulates Paraquat-Induced Epithelial to Mesenchymal Transition by Regulating Transforming Growth Factor-β (TGF-β) in A549 Cells

Paraquat (PQ), a widely used potent herbicide, generates superoxide anions and other free radicals, leading to severe toxicity and acute lung injury. PQ induces pulmonary fibrosis through epithelial to mesenchymal transition (EMT) characterized by increased number of myofibroblasts. Time-dependent PQ-induced EMT has been evaluated in present investigation where intracellular ROS levels were significantly enhanced after 24h of PQ intoxication. Anti-inflammatory effects of curcumin have been studied where alveolar epithelial cells (A549 cells) were incubated with curcumin (30 mu Mu) for 1 and 3h before PQ intoxication (700 mu M). Western blot and immunocytochemistry studies revealed that pretreatment of A549 cells with curcumin for 3h before PQ exposure has maintained E-cadherin expression and inhibited PQ induced alpha-smooth-muscle actin (alpha-SMA) expression. Transforming growth factor-beta (TGF-beta) that seems to be involved in PQ-induced EMT was enhanced after PQ intoxication, but curcumin pretreatment has effectively inhibited its expression. Immunostaining studies have shown that curcumin pretreatment has significantly reduced matrix metalloproteinase-9 (MMP-9) expressions, which were elevated after PQ intoxication. These results demonstrate that curcumin can regulate PQ-induced EMT by regulating the expression of TGF-beta.