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

被引:11
作者
Andersson, AK [1 ]
Thorvaldson, L [1 ]
Carlsson, C [1 ]
Sandler, S [1 ]
机构
[1] Uppsala Univ, Biomedicum, Dept Med Cell Biol, SE-75123 Uppsala, Sweden
关键词
islets of Langerhans; type; 1; diabetes; interleukin-1; beta; nitric oxide; iNOS; prostaglandin E-2;
D O I
10.1016/j.mce.2004.04.004
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:21 / 29
页数:9
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