Il-2 Gene-Expression and Nf-Kappa-B Activation Through Cd28 Requires Reactive Oxygen Production by 5-Lipoxygenase
1995 (English)In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 14, no 15, 3731-3740 p.Article in journal (Refereed) Published
Activation of the CD28 surface receptor provides a major costimulatory signal for T cell activation resulting in enhanced production of interleukin-2 (IL-2) and cell proliferation. In primary T lymphocytes we show that CD28 ligation leads to the rapid intracellular formation of reactive oxygen intermediates (ROIs) which are required for CD28-mediated activation of the NF-kappa B/CD28-responsive complex and IL-2 expression. Delineation of the CD28 signaling cascade was found to involve protein tyrosine kinase activity, followed by the activation of phospholipase Az and 5-lipoxygenase. Our data suggest that lipoxygenase metabolites activate ROI formation which then induce IL-2 expression via NF-KB activation. These findings should be useful for therapeutic strategies and the development of immunosuppressants targeting the CD28 costimulatory pathway.
Place, publisher, year, edition, pages
1995. Vol. 14, no 15, 3731-3740 p.
cd28, costimulation, human monocytes, il-2, lymphocytes-t, mediated suppression, molecule cd28, nf-kappa-b, nuclear factor, pathway, receptor, roi, t-cell activation, transcription, tumor-necrosis-factor
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:liu:diva-87079ISI: A1995RN94300015OAI: oai:DiVA.org:liu-87079DiVA: diva2:584835