Differential transcriptional expression of PPARalpha, PPARgamma1, and PPARgamma2 in the peritoneal macrophages and T-cell subsets of non-obese diabetic mice

J Clin Immunol. 2009 Sep;29(5):595-602. doi: 10.1007/s10875-009-9300-1. Epub 2009 May 27.

Abstract

Background: The peroxisome proliferator-activated receptors (PPARs) have been implicated in immune regulation. We determined the transcriptional expression of the three isoforms, PPARalpha, PPARgamma1, and PPARgamma2 in the peritoneal macrophages, CD4- and CD8-positive lymphocytes in non-obese diabetic (NOD) mice at 5 and 10 weeks of age as well as at diabetic stage.

Results: Compared to the non-obese diabetic resistant (NOR) mice, the peritoneal macrophages of NOD mice expressed increased levels of PPARalpha but reduced levels of PPARgamma2, while PPARgamma1 expression was unchanged in all age groups. CD4-positive lymphocytes expressed low levels of PPARalpha in diabetic NOD mice and greatly reduced expression of PPARgamma2 in all age groups. Unlike peritoneal macrophages and CD4-positive cells, the CD8-positive cells expressed low levels of PPARgamma1 in diabetic NOD mice but no difference in PPARalpha and PPARgamma2 expression was observed compared to NOR mice.

Conclusion: The current findings may suggest an important regulatory role of PPARs in the pathogenesis of autoimmune diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / pathology
  • Cells, Cultured
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetes Mellitus, Type 1 / pathology
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / metabolism
  • Macrophages, Peritoneal / pathology
  • Mice
  • Mice, Inbred NOD
  • PPAR alpha / genetics
  • PPAR alpha / immunology
  • PPAR alpha / metabolism*
  • PPAR gamma / genetics
  • PPAR gamma / immunology
  • PPAR gamma / metabolism*
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / immunology
  • Transcription Factors / metabolism*

Substances

  • PPAR alpha
  • PPAR gamma
  • Transcription Factors
  • peroxisome-proliferator-activated receptor-gamma coactivator-1