PPAR-γ agonists inhibit production of monocyte inflammatory cytokines

• Published in: Nature (London) Vol. 391; no. 6662; pp. 82 - 86
• Main Authors: Seed, Brian, Jiang, Chengyu, Ting, Adrian T
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.01.1998; Nature Publishing Group
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Arthritis; Biological and medical sciences; Cell Line; Cells; Chromans - pharmacology; Cytokines - biosynthesis; Cytokines - genetics; Fundamental and applied biological sciences. Psychology; Hormones; Humans; Immune system; Inflammation; Inflammation Mediators; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Molecular and cellular biology; Promoter Regions, Genetic; Prostaglandin D2 - analogs & derivatives; Prostaglandin D2 - pharmacology; Receptors, Cytoplasmic and Nuclear - agonists; Receptors, Cytoplasmic and Nuclear - physiology; Thiazoles - pharmacology; Thiazolidinediones; Transcription Factors - agonists; Transcription Factors - physiology; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - physiology; Human; Agonist; Nuclear receptor; Mononuclear cell; Cytokine; Biosynthesis; Inflammation; Transcription factor; In vitro
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/34184

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 repression,. Expression of PPAR-γ is an early and pivotal event in the differentiation of adipocytes. Several agents that promote differentiation of fibroblast lines into adipocytes have been shown to be PPAR-γ agonists, including several prostanoids, of which 15-deoxy-Δ,-prostaglandin J2 is the most potent,, as well as members of a new class of oral antidiabetic agents, the thiazolidinediones, and a variety of non-steroidal anti-inflammatory drugs (NSAIDs). 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).