Cytochrome P450 (CYP) epoxygenases have been considered the main producers of epoxyeicosatrienoic acids (EETs) through the oxidation of arachidonic acid (AA). EETs display various biological properties, notably their powerful anti-inflammatory activities. In the brain, EETs have proven to be neuroprotective and to improve neuroinflammation. However, it is known that inflammation could modify CYP expression. We have previously reported that an inflammatory process in astrocytes is able to down-regulate CYP2J3 and CYP2C11 mRNA, protein levels, and activity (Navarro-Mabarak et al., 2019). In this work, we evaluated the effect of neuroinflammation in protein expression of CYP epoxygenases in the brain. Neuroinflammation was induced by the intraperitoneal administration of LPS (1 mg/kg) to male Wistar rats and was corroborated by IL-6, GFAP, and Iba-1 protein levels in the cortex over time. CYP2J3 and CYP2C11 protein levels were also evaluated in the cortex after 6, 12, 24, 48, and 72 h of LPS treatment. Our results show for the first time that neuroinflammation is able to downregulate CYP2J3 and CYP2C11 protein expression in the brain cortex.

细胞色素 P450 (CYP) 加氧酶被认为是通过花生四烯酸 (AA) 氧化产生环氧二十碳三烯酸 (EET) 的主要生产者。EET 显示出各种生物学特性，尤其是其强大的抗炎活性。在大脑中，EET 已被证明具有神经保护作用并能改善神经炎症。然而，众所周知，炎症可以改变 CYP 的表达。我们之前曾报道，星形胶质细胞的炎症过程能够下调 CYP2J3 和 CYP2C11 mRNA、蛋白质水平和活性（Navarro-Mabarak 等，2019）。在这项工作中，我们评估了神经炎症对大脑中 CYP 环氧化酶蛋白表达的影响。对雄性 Wistar 大鼠腹腔注射 LPS (1 mg/kg) 诱导神经炎症，IL-6、GFAP、随着时间的推移，皮层中的 Iba-1 蛋白水平。在 LPS 治疗 6、12、24、48 和 72 小时后，还在皮质中评估了 CYP2J3 和 CYP2C11 蛋白水平。我们的结果首次表明，神经炎症能够下调大脑皮层中 CYP2J3 和 CYP2C11 蛋白的表达。