Glutathione depletion is involved in the inhibition of procollagen α1(I) mRNA levels caused by TNF-α on hepatic stellate cells

TNF-α has been shown to inhibit procollagen α1(I) expression in hepatic stellate cells (HSC), although the molecular mechanisms involved have not been fully established. In the present work, we studied the possible role played by oxidative stress and NFκB on the antifibrogenic action of TNF-α on a cell line of rat HSC. Treatment of HSC with TNF-α did not affect either intracellular levels of reactive oxygen species or lipid peroxidation, but caused a decrease on reduced glutathione (GSH) levels. Restoration of intracellular GSH by incubation with exogenous GSH prevented the inhibition of procollagen α1(I) levels caused by TNF-α. The effect of GSH was not mimicked by antioxidants like deferoxamine, tempol or trolox. Activation of NFκB by TNF-α was also abolished by preincubation of HSC with GSH, but not by deferoxamine, tempol or trolox. These results point to GSH depletion as a mediator of TNF-α action in HSC.