15d-Deoxy-Δ12,14-prostaglandin J2 modulates collagen type I synthesis in human hepatic stellate cells by inducing oxidative stress

15 deoxy-Δ12,14-prostaglandin2 (15d-PGJ2) is known to inhibit the proliferation of hepatic stellate cells (HSCs), major cellular components that cause hepatic fibrosis, in vitro. It also induces oxidative stress, which results in hepatic myofibroblast death. On the other hand, oxidative stress generally induces HSC proliferation and collagen synthesis in vitro, and liver fibrogenesis in vivo. In this study, we evaluated the effects of 15d-PGJ2 at various concentrations on the viability and collagen synthesis of HSCs. 15d-PGJ2 increased intracellular reactive oxygen species (ROS), and reduced the viability of human HSCs at concentrations ⩾5 μM by inducing apoptotic cell death. In addition, the antioxidants α-tocopherol and N-acetylcysteine (NAC) blocked 15d-PGJ2-induced HSC death. Collagen I synthesis was increased 1.5-fold by 0.5 μM 15d-PGJ2 treatment, but was reduced to 30% of the control level by 10 μM 15d-PGJ2, and NAC pretreatment prevented these changes in collagen production by 15d-PGJ2. We conclude that 15d-PGJ2 may either induce or prevent hepatic fibrogenesis depending on its concentration.