Effect of nintedanib, pirfenidone, N-acetylcysteine and their combinations on cultured myofibroblast-type cells derived from patients with asbestosis and idiopathic pulmonary fibrosis

Abstract

Myofibroblasts and extracellular matrix deposition involve in the pathogenesis of interstitial lung diseases (ILD). Nintendanib and pirfenidone are new pharmacological treatments for idiopathic pulmonary fibrosis (IPF) but it is unknown if nintedanib, pirfenidone or N-acetylcysteine (NAC) has any effect on other type of fibrotic ILDs. The aim was to study the effects of nintedanib, pirfenidone and NAC individually or combined on cultured stromal cells derived from patients with IPF, asbestosis or normal lung. Fibroblastic cells cultured from lung tissue samples (n=6) were exposured to transforming growth factor-beta 1 (TGF-β1) and treated afterwards with the drugs or their different combinations. The gene expression of alpha smooth muscle actin (α-SMA), fibronectin, collagen type I, tenascin C and matrix metalloproteinase 2 (MMP2) was measured by quantitative RT-PCR. Viability of the cells was analyzed with MTT-assay. In all tested cell types TGF-β1 induced α-SMA expression indicating myofibroblast differentiation. α-SMA expression was mainly reduced most efficiently by drug combinations of two or three drugs (Figure 1.). Similar effect was also seen in fibronectin and collagen type I expression. We conclude that cultured cells from IPF, asbestosis or normal lung have similar responses for pirfenidone, nintedanib and NAC.