Modulation of TH1 differentiation  Peroxisome Proliferator–Activated  Receptor?–Independent Manner

Eugene S. Attakpa; Alphonse Sezan; Lamine Baba– Moussa; Bialli Seri

Volume : II, Issue : IX, September - 2013

Modulation of TH1 differentiation Peroxisome Proliferator–Activated Receptor?–Independent Manner

Eugene S. Attakpa, Alphonse Sezan, Lamine Baba Moussa, Bialli Seri

Abstract :

The influence of PPAR? on numerous biological activities arises through its ability to carry out gene regulation. We examined the effects of PPARα on the expression of on key transcription factors involved in Th cell differentiation, T–bet, and determined whether PPARα mediates its effects. The T–cells from PPAR?null mice secreted higher IFN? and lower IL–2 concentrations than WT T–cells. We demonstrate that PPAR??regulates the expression of these cytokines by CD4+ T cells, through its ability to negatively regulate TH1 differentiation via the transcription of T–bet both at mRNA and protein levels. T–cells from PPAR?null mice expressed higher p38 phosphorylation than WT T–cells. T–bet expression in CD4+ T cells was determined to be influenced by p38 mitogen–activated protein (MAP) kinase activation. The presence of WY14,643, PPAR?? suppressed the phosphorylation of p38 MAP kinase in both the cell types. The pharmacological inhibitors of MAP kinases also downregulated T–bet in T–cells.