Cytokine-induced PGE2 formation is reduced from iNOS deficient murine islets
2004 (English)In: Molecular and Cellular Endocrinology, ISSN 0303-7207, E-ISSN 1872-8057, Vol. 220, no 1-2, 21-29 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2004. Vol. 220, no 1-2, 21-29 p.
Islets of Langerhans, type 1 diabetes, interleukin-1β, nitric oxide, iNOS, prostaglandin E2
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-72025DOI: 10.1016/j.mce.2004.04.004ISI: 000222570100003PubMedID: 15196696OAI: oai:DiVA.org:uu-72025DiVA: diva2:99936