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

Biochem Biophys Res Commun. 1994 Aug 30;203(1):149-55. doi: 10.1006/bbrc.1994.2161.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Cell Nucleus / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Insulin / biosynthesis*
  • Interleukin-1 / pharmacology*
  • Molecular Sequence Data
  • NF-kappa B / metabolism*
  • Nitric Oxide / metabolism*
  • Nitrites / metabolism
  • Oligodeoxyribonucleotides
  • Rats
  • Recombinant Proteins / pharmacology
  • Subcellular Fractions / metabolism
  • Tosyllysine Chloromethyl Ketone / pharmacology*


  • Insulin
  • Interleukin-1
  • NF-kappa B
  • Nitrites
  • Oligodeoxyribonucleotides
  • Recombinant Proteins
  • Tosyllysine Chloromethyl Ketone
  • Nitric Oxide