PPAR-γ agonists inhibit production of monocyte inflammatory cytokines
PPAR-γ agonists inhibit production of monocyte inflammatory cytokines
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作者：
Jiang, CY;Ting, AT;Seed, B
过氧化物酶体增殖物激活受体-γ（PPAR-gamma）是转录因子的核受体家族的成员，其是介导配体依赖性转录激活和抑制的一个大的且多样的蛋白质组（1，2）。PPAR-gamma的表达是脂肪细胞分化中的早期和关键事件（3-6）。几种促进成纤维细胞系分化为脂肪细胞的药物已被证明是PPAR-γ激动剂（7-10），包括几种前列腺素类，其中15-脱氧-δ（12，14）-前列腺素J（2）是最有效的（8，9），以及一类新的口服抗糖尿病药物噻唑烷二酮类（7），和多种非甾体抗炎药（NSAID）（10）。在这里，我们表明，PPAR-gamma激动剂抑制单核细胞的炎症细胞因子在激动剂浓度相似，被发现是有效的促进脂肪形成。抑制细胞因子的产生可能有助于解释NSAID在治疗类风湿性关节炎中观察到的增量治疗获益，其血浆药物浓度显著高于抑制前列腺素G/H合酶（环氧合酶）所需的浓度。
The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) 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(1,2). Expression of PPAR-gamma is an early and pivotal event in the differentiation of adipocytes(3-6). Several agents that promote differentiation of fibroblast lines into adipocytes have been shown to be PPAR-gamma agonists(7-10), including several prostanoids, of which 15-deoxy-Delta(12,14)-prostaglandin J(2) is the most potent(8,9), as well as members of a new class of oral antidiabetic agents, the thiazolidinediones(7), and a variety of non-steroidal anti-inflammatory drugs (NSAIDs)(10). Here we show that PPAR-gamma 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).