Cross talk between PPARγ and NF-κB or between PPARγ and C/EBPβ. (A) Troglitazone inhibition of IL-6 transcription. C/EBPβ and NF-κB bind to the promoter region of the IL-6 gene and their cooperation is needed to activate IL-6 transcription. The nuclear receptor PPARγ can be activated by troglitazone. Predominately, the complex between C/EBPβ and troglitazone-bound PPARγ leads to decreased DNA binding and transactivation of C/EBPβ, in turn inhibiting gene expression of IL-6. In addition, PGC-1, a coactivator, is shared by both PPARγ and NF-κB. After activation by ligands, ligand-bound PPARγ competes for the limited amounts of PGC-1. Therefore, NF-κB dissociates with PGC-1 and decreases NF-κB DNA-binding and transactivation, leading to blocked IL-6 transcription. (B) 15-d-PGJ2 inhibition of IL-6 transcription. Although 15-d-PGJ2 also shares the above ligand-bound PPARγ down-regulation mechanisms on C/EBPβ and NF-κB, 15-d-PGJ2, compared with troglitazone, prefers to use PGC-1 as a bridging protein to associate with NF-κB. In addition, 15-d-PGJ2 inactivates NF-κB through decreasing phosphorylation of IKK and IκB.