The nuclear receptor peroxisome proliferator-activated receptor-α mediates the anti-inflammatory actions of palmitoylethanolamide
The nuclear receptor peroxisome proliferator-activated receptor-α mediates the anti-inflammatory actions of palmitoylethanolamide
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DOI：
10.1124/mol.104.006353
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发表时间：
2005-01-01
影响因子：
3.6
通讯作者：
Piomelli, D
中科院分区：
文献类型：
--
作者：
Lo Verme, J;Fu, J;Piomelli, D
棕榈酰乙醇胺（PEA）是棕榈酸和乙醇胺的天然酰胺，通过一种尚未表征的机制减轻疼痛和炎症。在这里，我们确定核受体过氧化物酶体增殖物激活受体-α（PPAR-alpha）作为负责PEA抗炎特性的分子靶点。PEA在体外以3.1 +/-0.4 μ M的EC 50值选择性激活PPAR-alpha，并且当局部应用于小鼠皮肤时诱导PPAR-alpha mRNA的表达。在两种动物模型中，角叉菜胶诱导的爪水肿和佛波酯诱导的耳水肿，PEA减轻野生型小鼠的炎症，但对PPAR-alpha缺乏的小鼠没有作用。天然PPAR-alpha激动剂油酰乙醇胺（OEA）和合成PPAR-alpha激动剂GW 7647和Wy-14643以PPAR-alpha依赖性方式模拟这些作用。这些发现表明，PPAR-alpha介导PEA的抑制作用，并表明这种脂肪酸乙醇酰胺可能与其类似物OEA一样，作为PPAR-alpha的内源性配体。
Palmitoylethanolamide ( PEA), the naturally occurring amide of palmitic acid and ethanolamine, reduces pain and inflammation through an as-yet-uncharacterized mechanism. Here, we identify the nuclear receptor peroxisome proliferator-activated receptor-alpha ( PPAR-alpha) as the molecular target responsible for the anti-inflammatory properties of PEA. PEA selectively activates PPAR-alpha in vitro with an EC50 value of 3.1 +/- 0.4 muM and induces the expression of PPAR-alpha mRNA when applied topically to mouse skin. In two animal models, carrageenan-induced paw edema and phorbol ester-induced ear edema, PEA attenuates inflammation in wild-type mice but has no effect in mice deficient in PPAR-alpha. The natural PPAR-alpha agonist oleoylethanolamide (OEA) and the synthetic PPAR-alpha agonists GW7647 and Wy-14643 mimic these effects in a PPAR-alpha-dependent manner. These findings indicate that PPAR-alpha mediates the antiinflammatory effects of PEA and suggest that this fatty-acid ethanolamide may serve, like its analog OEA, as an endogenous ligand of PPAR-alpha.