Cytokine-induced PGE(2) formation is reduced from iNOS deficient murine islets.
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.
Andersson
Annika K
AK
Department of Medical Cell Biology, Uppsala University, Biomedicum, P.O. Box 571, Uppsala SE-75123, Sweden. annika.andersson@medcellbiol.uu.se
Thorvaldson
Lina
L
Carlsson
Carina
C
Sandler
Stellan
S
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis* / Q000494:pharmacology; D017353:Gene Deletion; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000172:deficiency* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism
D007328:Insulin; D007375:Interleukin-1; D007527:Isoenzymes; D012333:RNA, Messenger; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone