Peroxisome proliferator-activated receptor-gamma (PPAR-) plays a central role in whole body metabolism by regulating adipocyte differentiation and energy storage. Recently, however, PPAR- has also been demonstrated to affect proliferation, differentiation and apoptosis of different cell types. As we had previously showed that BAY 11-7085-induced synovial fibroblast apoptosis is prevented by PPAR- agonist 15d-PGJ2, the expression of PPAR- in these cells was studied. Both PPAR-1 and PPAR-2 isoforms were cloned from synovial fibroblast RNA, but only PPAR-{gamma 1} was detected by Western blot, showing constitutive nuclear expression. Within minutes of BAY 11-7085 treatment, PPAR-1 specific band was shifted into a form of higher mobility, suggesting dephosphorylation, as confirmed by phosphatase treatment of cell extracts. Of interest, BAY 11-7085-induced PPAR-1 dephosphorylation was followed by PARP and caspase-8 cleavage as well as by PPAR-1 protein degradation. PPAR-1 dephosphorylation was followed by the lost of PPAR-DNA-binding activity ubiquitously present in synovial fibroblast nuclear extracts. Unlike the phosphorylated form, dephosphorylated PPAR-1 was found in insoluble membrane cell fraction and it was not ubiquitinated before degradation. PPAR-1 dephosphorylation coincided with ERK1/2 phosphorylation that accompanies BAY 11-7085-induced synovial fibroblasts apoptosis. 15d-PGJ2, PGD2 and partially UO126, downregulated ERK1/2 phosphorylation, protected cells from BAY 11-7085-induced apoptosis, and reversed both PPAR-1 dephosphorylation and degradation. Furthermore, {PPAR-gamma} antagonist BADGE induced PPAR-1 degradation, ERK1/2 phosphorylation, and synovial fibroblasts apoptosis. The results presented suggest an anti-apoptotic role for PPAR-1 in synovial fibroblasts. Since apoptotic marker PARP is cleaved after PPAR-1 dephosphorylation but before PPAR-1 degradation, dephosphorylation event might be enough to mediate BAY 11-7085-induced apoptosis in synovial fibroblasts.