Direct administration of interleukin-1 and interferon-gamma to rat pancreas leads to the in vivo production of nitric oxide and expression of inducible nitric oxide synthase and inducible cyclooxygenase

Citation
T. Tabatabaie et al., Direct administration of interleukin-1 and interferon-gamma to rat pancreas leads to the in vivo production of nitric oxide and expression of inducible nitric oxide synthase and inducible cyclooxygenase, PANCREAS, 23(3), 2001, pp. 316-322
Citations number
48
Language
INGLESE
art.tipo
Article
Categorie Soggetti
da verificare
Journal title
PANCREAS
ISSN journal
0885-3177 → ACNP
Volume
23
Issue
3
Year of publication
2001
Pages
316 - 322
Database
ISI
SICI code
0885-3177(200110)23:3<316:DAOIAI>2.0.ZU;2-O
Abstract
Introduction: Proinflammatory cytokines may play a pivotal role in the path ogenesis of insulin-dependent diabetes mellitus (IDDM). In vitro, the forma tion of nitric oxide (NO) catalyzed by inducible NO synthase (iNOS) has bee n shown to be involved in the cytotoxic effects of cytokines on pancreatic beta cells. Cytokines have also been shown to cause the expression of induc ible cyclooxygenase (COX-2) in isolated islets. Aims: To describe a novel in vivo model that allows investigation of the ef fects of direct cytokine administration to the pancreas. Methodology and Results: By using this method, we demonstrate that administ ration of interleukin-1 beta and interferon-gamma to rat pancreas results i n the generation of NO in the treated pancreata as detected by NO trapping and electron paramagnetic resonance spectroscopy. beta cells were identifie d as the source of the formed NO. Reverse transcription and polymerase chai n reaction analyses showed that administration of cytokines to the pancreas leads to the expression of iNOS and COX-2 mRNA in the pancreas tissue as w ell as the islets isolated from such tissues. The compound phenyl N-tert-bu tylnitrone, Which protects mice against streptozotocin-induced IDDM, inhibi ts NO formation and downregulates both iNOS and COX-2 mRNA levels.