Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor.
Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor.
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DOI：
10.1038/s41598-017-00342-1
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发表时间：
2017-03-23
影响因子：
4.6
通讯作者：
Maione S
中科院分区：
文献类型：
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作者：
Guida F;Luongo L;Boccella S;Giordano ME;Romano R;Bellini G;Manzo I;Furiano A;Rizzo A;Imperatore R;Iannotti FA;D'Aniello E;Piscitelli F;Sca Rossi F;Cristino L;Di Marzo V;de Novellis V;Maione S
内源性脂肪酸酰胺棕榈酰乙醇酰胺（PEA）已被证明主要通过抑制肥大细胞、单核细胞和巨噬细胞释放促炎分子来发挥抗炎作用。内源性大麻素（eCB）系统的间接激活是已经提出的几种作用机制之一，这些机制是PEA体内不同作用的基础。在这项研究中，我们使用培养的大鼠小胶质细胞和人类巨噬细胞，以评估是否PEA影响eCB信号。PEA可通过激活过氧化物酶体增殖物激活受体α（peroxisome proliferator-activated receptor-α，PPAR-α），促进CB 2 mRNA和蛋白表达。这种新的基因调控机制通过以下方式得到证实：（i）药物学上的PPAR-α操纵，（ii）PPAR-α mRNA沉默，（iii）染色质免疫沉淀。此外，暴露于PEA诱导与反应性小胶质细胞表型相关的形态学变化，包括增加的吞噬作用和迁移活性。我们的研究结果表明，间接调节小胶质细胞CB 2 R的表达作为一个新的可能的机制PEA的影响。PEA可作为预防/治疗CNS疾病中与神经炎症相关的症状的有用工具进行探索。
The endogenous fatty acid amide palmitoylethanolamide (PEA) has been shown to exert anti-inflammatory actions mainly through inhibition of the release of pro-inflammatory molecules from mast cells, monocytes and macrophages. Indirect activation of the endocannabinoid (eCB) system is among the several mechanisms of action that have been proposed to underlie the different effects of PEA in vivo. In this study, we used cultured rat microglia and human macrophages to evaluate whether PEA affects eCB signaling. PEA was found to increase CB2 mRNA and protein expression through peroxisome proliferator-activated receptor-α (PPAR-α) activation. This novel gene regulation mechanism was demonstrated through: (i) pharmacological PPAR-α manipulation, (ii) PPAR-α mRNA silencing, (iii) chromatin immunoprecipitation. Moreover, exposure to PEA induced morphological changes associated with a reactive microglial phenotype, including increased phagocytosis and migratory activity. Our findings suggest indirect regulation of microglial CB2R expression as a new possible mechanism underlying the effects of PEA. PEA can be explored as a useful tool for preventing/treating the symptoms associated with neuroinflammation in CNS disorders.