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
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
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.