Resveratrol amplifies profibrogenic effects of free fatty acids on human hepatic stellate cells

Aim: To ascertain whether resveratrol affects the expression of free fatty acids (FFA)‐induced profibrogenic genes, death receptors, and/or apoptosis‐related molecules in human hepatic stellate cells, using the LX‐2 cell line. Methods: Cells were cultured in the presence of FFAs (2:1 oleate : palmitate) and subsequently treated with resveratrol. Gene expression rates were determined by quantitative real‐time PCR. The 50% lethal dose (LD50) of resveratrol in the presence of FFAs was assessed with the MTT viability test. Results: Compared to vehicle controls, incubation of LX‐2 cells with 0.5 mM FFAs induced profibrogenic genes (α‐SMA × 2.9; TGF‐β1 × 1.6; TIMP‐1 × 1.4), death receptors (CD95/Fas × 3.8; TNFR‐1 × 1.4), and anti‐apoptotic molecules (Bcl‐2 × 2.3; Mcl‐1 × 1.3). Subsequent addition of 15 µM resveratrol (LD50 = 23.2 µM) significantly (P