[Retracted] A Role for PPAR in the Regulation of Cytokines in Immune Cells and Cancer
Figure 2
PPAR regulation of cytokine-mediated immunoregulatory
circuit between monocytes/macrophages and T lymphocytes. T helper (Th)
lymphocytes can be traditionally divided into two functional subsets consisting
of Th1 and Th2 cells on the basis of the immunoregulatory cytokines
that these T cells produce. Thp cells are the pluripotent precursors
of Th1 and Th2 cells. IL-4 is principally produced by helper T cells of theTh2 phenotype. IL-4
can induce the upregulation of expression of the enzyme 12/15 lipoxygenase in
monocytes/macrophages, providing a potential PPAR-specific ligands 13-HODE. The mediator
secreted by monocytes can be taken up by neighboring Thp or Th1 cells and
activate PPAR in these cells. Since NFAT and NF-κB
bind to the promoter region of the IL-2 gene and are needed to activate IL-2
transcription in T cells, the ligand-dependent binding of PPAR to NFAT and NF-κB correlates the dissociation of NFAT
and NF-κB from IL-2 promoter, thus inhibiting gene expression of IL-2 in Thp
or Th1 cells.