The peroxisome proliferator-activated receptor-γ (PPAR-γ) is a member of the nuclear receptor family of transcription factors, a large and diverse group of proteins that mediate ligand-dependent transcriptional activation and repression1,2. Expression of PPAR-γ is an early and pivotal event in the differentiation of adipocytes3,4,5,6. Several agents that promote differentiation of fibroblast lines into adipocytes have been shown to be PPAR-γ agonists7,8,9,10, including several prostanoids, of which 15-deoxy-Δ12,14-prostaglandin J2 is the most potent8,9, as well as members of a new class of oral antidiabetic agents, the thiazolidinediones7, and a variety of non-steroidal anti-inflammatory drugs (NSAIDs)10. Here we show that PPAR-γ agonists suppress monocyte elaboration of inflammatory cytokines at agonist concentrations similar to those found to be effective for the promotion of adipogenesis. Inhibition of cytokine production may help to explain the incremental therapeutic benefit of NSAIDs observed in the treatment of rheumatoid arthritis at plasma drug concentrations substantially higher than are required to inhibit prostaglandin G/H synthase (cyclooxygenase).
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We thank T. Gulick for advice, guidance, time and key reagents. This work was supported by a grant from Amgen, Inc., and awards from the NIH. A.T. is a fellow of the Cancer Research Institute.
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