Male and female NOD mice differentially express peroxisome proliferator-activated receptors and pathogenic cytokines

The peroxisome proliferator-activated receptors (PPARs) have been implicated in regulating the immune response. We determined the relative changes in the transcriptional expression of PPAR isoforms (alpha, gamma 1 and gamma 2) and cytokines involved in the pathogenesis of type 1 diabetes (T1D) in the immune cells of 5 weeks, 10 weeks and diabetic male non-obese diabetic (NOD) mice compared to those of female NOD mice from our previous studies, normalized against their respective non-obese diabetic resistant (NOR) mice controls. Overall PPAR alpha was significantly more elevated in the macrophages of female NOD mice of all age groups whereas PPAR gamma, particularly the PPAR gamma 2 isoform was more depressed in the macrophages and CD4(+) lymphocytes of female NOD mice compared to their male counterparts. The pro-inflammatory cytokines, IL-1 and TNF alpha, as well as the Th1 cytokines, IL-2 and IFN gamma were more elevated in female NOD mice whereas the Th2 cytokine, IL-4, was more depressed in these mice compared to their male counterparts. These findings suggest that the preponderance of T1D in female NOD mice may be influenced by the more pronounced changes in the expression of PPAR isoforms and pathogenic cytokines compared to those in male NOD mice. (C) 2010 Elsevier GmbH. All rights reserved.