Faculty Collaboration Database

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

Date

12/21/1993

Pubmed ID

7505613

DOI

10.1021/bi00213a002

Scopus ID

2-s2.0-0027788115 (requires institutional sign-in at Scopus site)   250 Citations

Abstract

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)

Author List

Corbett JA, Kwon G, Turk J, McDaniel ML

Author

John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Oxidoreductases
Animals
Arginine
Dactinomycin
Dinoprostone
Enzyme Activation
In Vitro Techniques
Interleukin-1
Islets of Langerhans
Kinetics
Male
Nitric Oxide
Nitric Oxide Synthase
Prostaglandin-Endoperoxide Synthases
Rats
Rats, Sprague-Dawley
omega-N-Methylarginine