Effects of oxidants and antioxidants on nuclear factor kappa B activation in three different cell lines: evidence against a universal hypothesis involving oxygen radicals.
A model for NF kappa B activation involving reactive oxygen intermediates has recently been proposed. We have explored this model in three cell lines, Jurkat T cells, EL4.NOB-1 T cells and KB epidermal cells using hydrogen peroxide and two physiological activators of NF kappa B, interleukin-1 (IL1) and tumor necrosis factor (TNF) as stimuli. In agreement with earlier studies hydrogen peroxide activated NF kappa B in Jurkat, although only at much higher concentrations (10 mM) than those previously reported. However, hydrogen peroxide failed to activate in the two other cell lines under a range of conditions. Similarly, N-acetylcysteine only proved inhibitory in hydrogen peroxide and TNF treated Jurkat and failed to inhibit IL1 and TNF-activated NF kappa B in EL4.NOB-1 and KB cells respectively. N-Acetylcysteine inhibited IL1-induced interleukin-2 in EL4, however, demonstrating that N-acetylcysteine was biologically active. These results suggest that the reactive oxygen model of NF kappa B activation may be cell-type restricted. In contrast to the results with N-acetylcysteine, the antioxidant and metal chelator, pyrolidine dithiocarbamate (PDTC) inhibited NF kappa B activation, although these effects may be unrelated to any antioxidant properties. PDTC also inhibited IL1-induced interleukin-2. Finally, studies with the pro-oxidant diamide showed that this could not activate NF kappa B in any of the cells and in contrast proved inhibitory. The results from this study therefore suggest that the reactive oxygen model of NF kappa B activation may be restricted to certain cell types and that the presence of such a system is not required for the activation of NF kappa B by IL1 and TNF.
Brennan
P
P
Biochemistry Department, Trinity College, Dublin, Ireland.
O'Neill
L A
LA
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005609:Free Radicals; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D005609:Free Radicals; D007375:Interleukin-1; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D010100:Oxygen; D000111:Acetylcysteine