Abstract
This study was performed to investigate whether peroxisome proliterator-activated receptor-γ (PPAR-γ) exerted an anti-inflammatory effect on rheumatoid synovial cells and inhibited dysregulated proliferation. The expression of PPAR-γ mRNA in cultured human synoviocytes and THP-1 cells was analysed by RT-PCR. PPAR-γ was expressed in normal, osteoarthritis (OA), rheumatoid arthritis (RA) synovial cells as well as a human monocytic cell line, THP-1. In RA and OA synoviocytes, the induction of inflammatory cytokine mRNA expression such as TNF-α and IL-1β was significantly inhibited by the natural PPAR-γ agonist, 15 deoxy-Δ12,14prostaglandin J2(15d-PGJ2). The effect of PPAR-γ on the nuclear factor (NF)-κB activity was tested by electrophoretic mobility shift assay (EMSA). Both troglitazone and 15d-PGJ2markedly inhibited TNF-α-induced NF-κB activation at 30μM. However, PPAR-γ agonist neither reduced proliferation nor induced apoptosis in RA synoviocytes when measured by XTT assay and fluorescence activated cell sorter (FACS) analysis. In contrast, it induced apoptosis in a dose-dependent manner in THP-1 cells and augmented TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis as well. In conclusion, these data demonstrate that PPAR-γ is expressed in human synoviocytes and THP-1 cells, and the PPAR-γ activation inhibits expression of inflammatory cytokines in RA synoviocytes. Furthermore, PPAR-γ activation induces apoptosis by itself and augments TRAIL/Apo2L-induced apoptosis in THP-1 cells. These results suggest that PPAR-γ agonists may provide a new therapeutic approach for RA.
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