Cytokine-induced PGE2 formation is reduced from iNOS deficient murine islets

• Published in: Molecular and cellular endocrinology Vol. 220; no. 1-2; pp. 21 - 29
• Main Authors: Andersson, Annika K, Thorvaldson, Lina, Carlsson, Carina, Sandler, Stellan
• Format: Journal Article
• Language: English
• Published: 31.05.2004
• Subjects: iNOS; interleukin-1β; Islets of Langerhans; MEDICIN; MEDICINE; nitric oxide; prostaglandin E2; type 1 diabetes
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2004.04.004

Cytokines may be involved in islet destruction during Type 1 diabetes. Exposure to interleukin-1beta (IL-1beta) or IL-1beta plus interferon-gamma (IFN-gamma) of rodent islets induces expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Subsequent formation of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) may impair beta-cell function. Using iNOS deficient (iNOS -/-) islets, we have further investigated the relation between NO formation and PGE(2) induction. We found that iNOS -/- islets responded with a reduced PGE(2) formation following IL-1beta or (IL-1beta + IFN-gamma) treatment compared to wild-type (wt) islets, while COX-2 mRNA or protein content were unchanged. By the addition of an NO donor together with IL-1beta, PGE(2) formation could be stimulated from iNOS -/- islets. We conclude that the lowered capacity of PGE(2) formation observed from cytokine exposed iNOS -/- islets is due to a decreased stimulation of PGE(2) formation by the COX-2 enzyme in the absence of NO, rather then differences in expressed COX-2 protein.