[Retracted] A Role for PPAR𝛾 in the Regulation of Cytokines in Immune Cells and Cancer

Figure 1

PPAR crosstalk with IL-6-activated STAT3 signaling pathway. Upon IL-6 binding, the IL-6R/gp130 dimer induces phosphorylation of JAK1,3, which in turn phosphorylates STAT3. The phosphorylated STAT3 dimerizes and translocates to the nucleues, where they bind to the STAT3 binding element (SBE) in the responsive gene to initiate transcription. Two structurally distinct PPAR agonists suppress IL-6-activated STAT3 through diverse molecular mechanisms. 15-d-PGJ2 enhances direct physical protein-protein interaction between PPAR and phosphorylated STAT3 and represses IL-6 signaling by inhibiting the binding of STAT3 to target promoters; Troglitazone inhibits the interaction between PPAR and the corepressor SMRT, thereby inducing the redistribution of SMRT from PPAR to activated STAT3, in turn transcriptionally inactivating STAT3 signaling.