Eicosanoid imbalance in the NOD mouse is related to a dysregulation in soluble epoxide hydrolase and 15-PGDH expression.
Eicosanoids promote or resolve inflammation depending on the class produced. Macrophage from nonobese diabetic (NOD) mouse produce increased proinflammatory lipid mediators and low levels of antiinflammatory lipoxin A4 (LXA4). The enhanced proinflammatory eicosanoids is secondary to increased cyclooxygenase-2 (Cox-2) expression and low levels of prostaglandin/leukotriene catabolic enzyme, 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Deficient LXA4 production is not due to deficient lipoxygenase (LO) activity, but is related to increased soluble epoxide hydrolase (sEH), involved in metabolism of anti-inflammatory epoxyeicosatrienoic acids (EET). These aberrations in eicosanoid biology suggest that inflammation in the NOD mouse is likely to be prolonged and robust and may contribute to type 1 diabetes (T1D) pathogenesis.
Rodriguez
Michelle
M
Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, 1600 SW Archer Road No. D11-41, Gainesville, FL 32610, USA. rodrigm@pathology.ufl.edu
Clare-Salzler
Michael
M
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015777:Eicosanoids / Q000276:immunology* / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D006911:Hydroxyprostaglandin Dehydrogenases / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D044045:Lipoxins / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D012995:Solubility
D015777:Eicosanoids; D008070:Lipopolysaccharides; D044045:Lipoxins; C040527:lipoxin A4; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D051546:Cyclooxygenase 2; D004851:Epoxide Hydrolases