Peroxisome proliferator-activated receptors in inflammation control
Peroxisome proliferator-activated receptors in inflammation control
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DOI：
10.1677/joe.0.1690453
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发表时间：
2001-06-01
影响因子：
4
通讯作者：
Staels, B
中科院分区：
文献类型：
--
作者：
Delerive, P;Fruchart, JC;Staels, B
过氧化物酶体增殖物激活受体（PPARs）是核受体超家族中的配体激活的转录因子。PPARalpha在肝脏、骨骼肌、肾脏、心脏和血管壁中高度表达。PPAR γ主要在脂肪组织、肠和巨噬细胞中检测到。PPARs被脂肪酸衍生物和药理学试剂如贝特类和格列酮激活，贝特类和格列酮分别对PPARalpha和PPARgamma具有特异性。PPARs调节脂质和脂蛋白代谢、葡萄糖稳态、细胞增殖和分化以及凋亡。PPARalpha控制细胞内和细胞外脂质代谢，而PPARgamma触发脂肪细胞分化并促进脂质储存。此外，PPARs还调节炎症反应。已经显示，PPAR激活剂通过抑制促炎基因如细胞因子、金属蛋白酶和急性期蛋白的表达，在各种细胞类型中发挥抗炎活性。PPARs通过拮抗AP-1、核因子-kappaB（NF-kappaB）、信号转导子和转录激活子以及活化的T细胞信号传导通路的核因子，以及通过刺激促炎性类花生酸的催化剂，负性调节炎症反应基因的转录。这些最近的发现表明PPARs在炎症中的调节作用，在慢性炎症性疾病中具有潜在的治疗应用。
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily. PPAR alpha is highly expressed in liver, skeletal muscle, kidney, heart and the vascular wall. PPAR gamma is predominantly detected in adipose tissue, intestine and macrophages. PPARs are activated by fatty-acid derivatives and pharmacological agents such as fibrates and glitazones which are specific for PPAR alpha and PPAR gamma respectively. PPARs regulate lipid and lipoprotein metabolism, glucose homeostasis, cell proliferation and differentiation, and apoptosis. PPAR alpha controls intra- and extracellular lipid metabolisms whereas PPAR gamma triggers adipocyte differentiation and promotes lipid storage. In addition, PPARs also modulate the inflammatory response. PPAR activators have been shown to exert anti-inflammatory activities in various cell types by inhibiting the expression of proinflammatory genes such as cytokines, metalloproteases and acute-phase proteins. PPARs negatively regulate the transcription of inflammatory response genes by antagonizing the AP-1, nuclear factor-kappaB (NF-kappaB), signal transducer and activator of transcription and nuclear factor of activated T-cells signalling pathways and by stimulating the catabolism of proinflammatory eicosanoids. These recent findings indicate a modulatory role PPARs in inflammation with potential therapeutical applications in chronic inflammatory diseases.