CYTOKINES ACTIVATE THE NUCLEAR FACTOR KAPPA-B (NF-KAPPA-B) AND INDUCENITRIC-OXIDE PRODUCTION IN HUMAN PANCREATIC-ISLETS

We studied the ability of cytokines to activate the nuclear transcript ion factor NF-kappa B in human pancreatic islets and the putative role of NF-kappa B for cytokine-induced NO production. Brief exposure (20 min) of human islets of Langerhans to a combination of interleukin-1 b eta + interferon-gamma + tumor necrosis factor-alpha induced a 2.6-fol d increase in nuclear NF-kappa B activity in gel shift analysis. This increase was prevented by the NF-kappa B inhibitor, pyrrolidine dithio carbamate (PDTC), which also counteracted NO production by human islet s exposed for 14 h to the cytokine combination. High concentrations of interleukin-1 beta alone (150 and 250 U/ml) increased NF-kappa B nucl ear binding but faded to induce NO formation in human islets. The pres ent data are the first to demonstrate that cytokines activate NF-kappa B in primary adult human pancreatic islets and suggest that activatio n of NF-kappa B may be a necessary but not sufficient signal for cytok ine-induced iNOS expression in human islets of Langerhans.