Interleukin-1 beta induced activation of NF-kappa B in insulin producing RINm5F cells is prevented by the protease inhibitor N alpha-p-tosyl-L-lysine chloromethylketone.
The cytokine Interleukin-1 beta (IL-1 beta) is known to exert cytotoxic effects upon rodent beta-cells in vitro by inducing nitric oxide production and has therefore been suggested to play a role in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). Using the insulin producing rat cell line RINm5F and an electrophoretic mobility shift assay (EMSA), it was presently found that IL-1 beta induced a rapid activation (5 min) of the transcription factor NF-kappa B and that this event was prevented by the protease inhibitor N alpha-p-tosyl-L-lysine chloromethylketone (TLCK). TLCK prevented also IL-1 beta induced nitric oxide production. It is concluded that NF-kappa B activation may be a necessary signal for IL-1 beta induced beta-cell damage and that this process can be modulated by specific protease and NF-kappa B inhibitors.
Saldeen
J
J
Department of Medical Cell Biology, Uppsala University, Sweden.
Welsh
N
N
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007328:Insulin / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013347:Subcellular Fractions / Q000378:metabolism; D014107:Tosyllysine Chloromethyl Ketone / Q000494:pharmacology*
D007328:Insulin; D007375:Interleukin-1; D016328:NF-kappa B; D009573:Nitrites; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D014107:Tosyllysine Chloromethyl Ketone; D009569:Nitric Oxide