PURPOSE: IPF is characterized by over-abundant and over-activated fibroblasts. Curcumin inhibits scar tissue formation. We investigated the in vitro effects of curcumin on primary fibroblasts from IPF (IPF-F) and normal (normal-F) lungs, as well as pulmonary fibroblast (MRC-5), and epithelial (A549) cell lines.
METHODS: IPF-F and normal-F were isolated and exposed to curcumin in vitro. Cell viability analysis and quantitative-RT-PCR was conducted examining gene expression changes in alpha-SMA (ACTA2), extracellular matrix (ECM) component Collagen Type I Alpha 1 (COL1A1), Transforming Growth Factor Beta 1 (TGF-beta1, TGFB1), and Fibroblast Activation Protein (FAP).
RESULTS: Fibroblasts from 5 IPF lungs (N=3 patients), 5 normal lungs (N=3 donors) were studied in addition to MRC-5 and A549 cell lines. A significant dose-dependent reduction in cell number of IPF-F, normal-F and MRC-5 was observed. Specifically, after a 72-hour exposure to 40μM curcumin, cell viability was reduced by 48.60±15.2% in IPF-F (p=0.0160*), 45.96±11.89% in normal-F (p=0.0168*), 84.89±2.34% in MRC-5 (p=0.0019*), and 13.33±12.01% in A549 (p=0.2585). Within 5 days of in vitro exposure, the fibroblasts became rounded and detached, indicative of apoptosis. In IPF-F, quantitative-RT-PCR analysis showed significant reduction in gene expression of ACTA2 (74%±5.7 (p=0.0075*)), COL1A1 (80±7.6% (p=0.0083*)), TGFB1 (87±16.4% (p=0.0192*)) and FAP (53±15% (p=0.0346*)) within 72 hours exposure to 60μM curcumin.
CONCLUSION: Curcumin exposure was associated with significant dose-dependent reductions in fibroblasts number, potentially due to inhibition of proliferation and/or induction of apoptosis. IPF-F had significant dose-dependent reduction in fibroblast activation markers, indicating potential deactivation of these cells and reduction in ECM component, which is supportive of downstream functionality. The epithelial A549 cells showed comparative insensitivity to curcumin, suggesting epithelial cell resistance and fibroblast-specific sensitivity.
CLINICAL IMPLICATIONS: This data highlights the efficacy and fibroblast cell specificity of curcumin and supports further investigation of this agent as a potential therapy for IPF.
DISCLOSURE: Mantej Chhina, No Financial Disclosure Information; No Product/Research Disclosure Information