Interleukin-1 signaling is dependent on free thiols.
Stimulation of the Interleukin-1 receptor type I (IL-1-RI) with IL-1 activates an associated serine/threonine kinase, IRAK, which phosphorylates downstream targets, resulting in NFkappaB activation. The signaling cascade is accompanied by oxidative processes and contains putative targets for redox regulation. Preincubation of the murine T cell line EL-4 and the human umbilical cord vein endothelial cell line ECV 304 with thiol modifying compounds like diamide, menadione or phenylarsine oxide inhibited the IL-1-induced phosphorylation of an endogenous substrate with a molecular mass of 60 kD. In the endothelial cell line, a second target of about 85 kD was phosphorylated after IL-1 stimulation, which was also inhibited by thiol modification. These data suggest that IL-1 signal transduction depends on free thiols which might be targets for redox regulation not only in lymphocytes, but also in endothelial cells.
Böl
G F
GF
German Institute of Human Nutrition, Department of Vitamins and Atherosclerosis, Potsdam-Rehbrücke. boel@www.dife.de
Tewes
F
F
Brigelius-Flohé
R
R
D000818:Animals; D001152:Arsenicals / Q000494:pharmacology; D002478:Cells, Cultured; D003958:Diamide / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008970:Molecular Weight; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D010766:Phosphorylation; D017472:Receptors, Interleukin-1 / Q000187:drug effects / Q000502:physiology*; D053573:Receptors, Interleukin-1 Type I; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D013945:Thymoma; D013953:Thymus Neoplasms; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins; D014812:Vitamin K / Q000494:pharmacology
D001152:Arsenicals; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D016328:NF-kappa B; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D013438:Sulfhydryl Compounds; C029341:oxophenylarsine; D003958:Diamide; D014812:Vitamin K