Cytokines activate the nuclear factor kappa B (NF-kappa B) and induce nitric oxide production in human pancreatic islets.
We studied the ability of cytokines to activate the nuclear transcription factor NF-kappaB in human pancreatic islets and the putative role of NF-kappaB for cytokine-induced NO production. Brief exposure (20 min) of human islets of Langerhans to a combination of interleukin-1beta + interferon-gamma + tumor necrosis factor-alpha induced a 2.6-fold increase in nuclear NF-kappaB activity in gel shift analysis. This increase was prevented by the NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), which also counteracted NO production by human islets exposed for 14 h to the cytokine combination. High concentrations of interleukin-1beta alone (150 and 250 U/ml) increased NF-kappaB nuclear binding but failed to induce NO formation in human islets. The present data are the first to demonstrate that cytokines activate NF-kappaB in primary adult human pancreatic islets and suggest that activation of NF-kappaB may be a necessary but not sufficient signal for cytokine-induced iNOS expression in human islets of Langerhans.
Flodström
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M
Department of Medical Cell Biology, Uppsala University, Sweden. malin.flodstrom@medcellbriol.uu.se
Welsh
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Eizirik
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D000293:Adolescent; D000328:Adult; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013859:Thiocarbamates / Q000494:pharmacology
D016207:Cytokines; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D009569:Nitric Oxide; D004247:DNA