EFFECTS OF ANTIOXIDANT ENZYME MODULATIONS ON INTERLEUKIN-1-INDUCED NUCLEAR FACTOR KAPPA-B ACTIVATION

Nuclear factor kappa B (NF-kappa B) is a potent and pleiotropic transc ription factor that can be activated by a wide variety of inducers, in cluding interleukin-1 (IL-1). Although the detailed activation mechani sm of NF-kappa B is still under investigation, it requires both phosph orylation and degradation of its inhibitory subunit I kappa B and the presence of an oxidative environment. In this study, we systematically evaluated the influence of glutathione peroxidase, glutathione reduct ase and catalase on IL-1-induced NF-kappa B activation by analysing th e effect of specific inhibitors of these enzymes. For the three antiox idant enzymes mentioned, their inhibition correlated with an overactiv ation of NF-kappa B, particularly for glutathione peroxidase. Inversel y, we tested the response of glutathione peroxidase transfected cells on NF-kappa B activation, which was lower as compared with the parenta l cells. Furthermore, interleukin-6 production also correlated perfect ly with the reduced level of NF-kappa B activation in these experiment s. The results clearly show that NF-kappa B activation is, strongly de pendent on the antioxidant potential of the cells, especially on the a ctivity of reduced glutathione-dependent enzymes such as glutathione p eroxidase. The results support the hypothesis that the level of the ox idised glutathione:reduced glutathione ratio and the activity of intra cellular antioxidant enzymes play a major role in NF-kappa B fine tuni ng. Copyright (C) Elsevier Science Inc.