Effects of palmitoylethanolamide on immunologically induced histamine, PGD2 and TNFα release from canine skin mast cells

Effects of palmitoylethanolamide on immunologically induced histamine, PGD2 and TNFα release from canine skin mast cells
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DOI:
10.1016/j.vetimm.2009.06.011
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发表时间:
2010-01-15
影响因子:
1.8
通讯作者:
Puigdemont, A.
Puigdemont, A.
中科院分区:
农林科学3区
文献类型:
--
作者:
Cerrato, S.;Brazis, P.;Puigdemont, A.

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棕榈酰乙醇酰胺 (PEA) 是一种内源性大麻素样化合物,是脂肪酰胺家族的母体分子,脂肪酰胺家族是一组脂肪酸酰胺,能够通过下调肥大细胞脱颗粒发挥作用。 PEA 已被证明具有镇痛和抗炎活性,最近的研究表明它能够减轻人类和动物炎症性皮肤病的临床症状。尽管其药理功效众所周知,但该家族化合物的作用机制仍不清楚。 为了更好地了解烯酰胺对狗的细胞作用,将从皮肤活检中新鲜分离的犬肥大细胞与富含 IgE 的血清一起孵育,并用抗犬 IgE 进行攻击。组胺、前列腺素 D-2 (PGD(2)) 和肿瘤坏死因子-α (TNF α) 的释放在存在或不存在增加浓度的 PEA(范围从 10(-8) M 到 10(-5) M)的情况下进行测量。由犬抗 IgE 免疫诱导的组胺、PGD(2) 和 TNF α 释放在 PEA 存在下显着受到抑制。在 3 x 10(-6) M PEA 浓度下观察到对组胺释放的最大抑制作用,实现了 54.3 +/- 5.2% 的抑制。 PGD​​(2) 释放在10(-5) M 和10(-6) M PEA 浓度下显着受到抑制,抑制率分别为25.5 +/- 10.2% 和14.6 +/- 5.6%。最后,PEA 在 10(-5) M 和 3 x 10(-6) M 浓度下分别抑制 TNF α 释放至 29.2 +/- 2.0% 和 22.1 +/- 7.2%。 本研究中获得的结果表明,烯酰胺 PEA 能够下调皮肤肥大细胞活化。因此,我们的研究结果表明,在炎症和疼痛临床研究中观察到的 PEA 的有益作用可能至少部分归因于它抑制预先形成的和新合成的肥大细胞介质释放的能力。 (C) 2009 Elsevier B.V. 保留所有权利。
Palmitoylethanolamide (PEA) is an endocannabinoid-like compound and the parent molecule of the aliamide family, a group of fatty acid amides able to act through the down-regulation of mast cell degranulation. PEA has been proven to exert both analgesic and anti-inflammatory activity, and recent studies have shown its ability in reducing clinical symptoms of inflammatory skin diseases, both in humans and in animals. Although its pharmacological efficacy is well known, the mechanism of action of this family of compounds is still unclear.To better understand the cellular effects of aliamides in dogs, canine mast cells freshly isolated from skin biopsies were incubated with IgE-rich serum and were challenged with anti-canine IgE. Histamine, prostaglandin D-2 (PGD(2)) and tumour necrosis factor-alpha (TNF alpha) release was measured in the presence and absence of increasing concentrations of PEA, ranging from 10(-8) M to 10(-5) M.Histamine, PGD(2) and TNF alpha release, immunologically induced by canine anti-IgE, were significantly inhibited in the presence of PEA. The maximum inhibitory effect on histamine release was observed at 3 x 10(-6) M PEA concentration achieving an inhibition of 54.3 +/- 5.2%. PGD(2) release was significantly inhibited at 10(-5) M and 10(-6) M PEA concentrations with 25.5 +/- 10.2% and 14.6 +/- 5.6% of inhibition, respectively. Finally, PEA inhibited TNF alpha release to 29.2 +/- 2.0% and 22.1 +/- 7.2%, at concentrations of 10(-5) M and 3 x 10(-6) M, respectively.The results obtained in the present study showed the ability of the aliamide PEA to down-modulate skin mast cell activation. Therefore, our findings suggest that the beneficial effect of PEA, observed in inflammation and pain clinical studies, could be due, at least in part, to its ability to inhibit the release of both preformed and newly synthesised mast cell mediators. (C) 2009 Elsevier B.V. All rights reserved.