THYMIC PEPTIDES INHIBIT NUCLEAR FACTOR KAPPA-B ACTIVATION IN HUMAN T-LYMPHOCYTES

Nuclear factor kappa B (NF-kappa B), which has been implicated in the regulation of gene transcription, is essential for the expression of g enes controlled by the long terminal repeat of human immunodeficiency virus type 1. Studies have shown that reactive oxygen species are invo lved in signal transduction pathways leading to NF-kappa B activation. We have reported that calf thymic peptides (TP) protect various cell types from oxidant injury. In this study, we determined the effects of TP on NF-kappa B activation in human T lymphocytes (Jurkat cells) ind uced by two stimuli: tumor necrosis factor alpha and phorbol 12-myrist ate 13-acetate. Activated NF-kappa B in nuclear extracts was measured by an electrophoretic mobility shift assay (EMSA) using P-32-labeled p robe. TP consistently exhibited a dose-dependent inhibition of NF-kapp a B activation induced by both stimuli. Supershift with specific antib odies to NF-kappa B subunits confirmed that the inducible retarded ban ds observed in the EMSA are p65-p50 heterodimer of the NF-kappa B/Rel protein. Our data suggest that TP may act via antioxidant mechanisms t o block NF-kappa B activation in Jurkat cells.