Protective effect of linoleic acid on IFN γ-induced cellular injury in primary culture hepatocytes

We have previously demonstrated that treatment of hepatocytes with IFN γ results a series of cellular injury processes, including DNA synthesis arrest, membrane breakage and apoptosis. In the present work, we show that IFN γ suppresses cellular respiration and protein synthesis in hepatocytes, and that cellular respiration suppression is an early event in the IFN γ-induced cellular injuries. Polyunsaturated fatty acids (PUFAs) increased cellular respiration of hepatocytes, but only linoleic acid showed some protective effect against IFN γ-induced cellular respiration suppression. Linoleic acid also reduced other IFN γ-mediated cellular injuries, including membrane breakage and protein synthesis inhibition. Like linoleic acid, fetal bovine serum also inhibited IFN γ-induced cellular damage. Increased NAD levels were found in both IFN γ-treated and non-treated hepatocytes following the addition of PUFAs, but clofibrate, a peroxisome proliferator, bromophenacyl bromide (BPB), an inhibitor of phospholipase, nordihydroguaiaretic acid (NDGA), an inhibitor of lipoxygenase, and arachidonic acid, a metabolite of linoleic acid, did not inhibit IFN γ-induced cellular injury. In addition, the combination of linoleic acid and IFN γ induced nitric oxide (NO) synthesis in hepatocytes. These results suggest that fatty acid may play an important role in liver homeostasis during chronic inflammatory states and sepsis.