IL-1 beta induces the coexpression of both nitric oxide synthase and cyclooxygenase by islets of Langerhans: activation of cyclooxygenase by nitric oxide

Biochemistry. 1993 Dec 21;32(50):13767-70. doi: 10.1021/bi00213a002.


Autoimmune diabetes is characterized by an early infiltration of lymphocytes into and around islets, which is followed by selective destruction of the insulin-secreting beta-cell. Cytokines released during this inflammatory reaction have been implicated as effector molecules which mediate beta-cell destruction. In vitro treatment of rat islets with the cytokine IL-1 beta results in an inhibition of glucose-stimulated insulin secretion that is mediated by the overproduction of nitric oxide. IL-1 beta also stimulates the production of the cyclooxygenase (COX) product prostaglandin E2 (PGE2). In this study we have examined the effects of IL-1 beta on both inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (iCOX) expression, and the direct effects of nitric oxide on the activity of COX. Treatment of rat islets with 5 units/mL IL-1 beta induces a similar time-dependent production of both nitrite and PGE2. IL-1 beta-induced nitrite and PGE2 production is attenuated by the NOS inhibitor NG-monomethyl-L-arginine (NMMA), but NMMA has no inhibitory effect on the expression of either iCOX or iNOS as determined by immunoprecipitation. Actinomycin D prevents IL-1 beta-induced iCOX and iNOS expression and the production of both nitrite and PGE2 by islets, suggesting that mRNA transcription is required for IL-1 beta-induced expression of both iNOS and iCOX. The effects of exogenous arachidonic acid on both constitutive COX (cCOX) and iCOX activity were also investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Oxidoreductases / biosynthesis*
  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Dactinomycin / pharmacology
  • Dinoprostone / metabolism
  • Enzyme Activation
  • In Vitro Techniques
  • Interleukin-1 / pharmacology*
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / enzymology
  • Islets of Langerhans / metabolism
  • Kinetics
  • Male
  • Nitric Oxide / pharmacology*
  • Nitric Oxide Synthase
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • omega-N-Methylarginine


  • Interleukin-1
  • Dactinomycin
  • omega-N-Methylarginine
  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase
  • Prostaglandin-Endoperoxide Synthases
  • Amino Acid Oxidoreductases
  • Dinoprostone