Inhibition of Apoptosis and Increase in TNF Production by N-Acetylcysteine

Fas antigen is a member of the tumor necrosis factor receptor family and transduces a lethal signal in Fas-sensitive cells. We previously demonstrated that the sensitivity of Fasmediated apoptosis was modulated by changing the intracellular gluthatione （GSH） level in human T lymphocytes. When the Fas-sensitive cells were incubated with N-acetylcysteine （NAC）, intracellular GSH was increased and Fas-mediated apoptosis was blocked. In this report, we examined whether lymphokine-activated-killer （LAK） activity is increased by NAC treatment via inhibition of Fas-mediated activation-induced cell death （AICD）. We previously established the Fas-resistant variant cell line JKT2D1R from the parental Fas-sensitive cell line Jurkat. AICD in JKT2D1R was markedly reduced. Induction of Fas antigen on the cell surface was confirmed after incubation of normal PBL with PHA and IL-2 for 7 days. After incubation with NAC, the intracellular GSH level was increased. In this context, surface expression of Fas, CD3 and HLA class I and intracellular expression of TIA-1 remained unchanged. However, production of TNF was markedly increased by NAC treatment. Therefore, the results suggest that LAK activity may be increased in terms of TNF production, most likely due to the inhibition of AICD. These results suggest that the increase of intracellular GSH induced by the administration of NAC may increase LAK activity and have clinical significance in tumor immunology.departmental bulletin pape