Expression of Cyp2c/Cyp2j subfamily members and oxylipin levels during LPS-induced inflammation and resolution in mice
Expression of Cyp2c/Cyp2j subfamily members and oxylipin levels during LPS-induced inflammation and resolution in mice
复制标题
DOI：
10.1096/fj.201901872r
复制
发表时间：
2019-12-01
期刊：
影响因子：
4.8
通讯作者：
Zeldin, Darryl C.
中科院分区：
文献类型：
--
作者：
Graves, Joan P.;Bradbury, J. Alyce;Zeldin, Darryl C.
炎症刺激，如细菌LPS，改变许多细胞色素P450的表达。CYP2C和CYP2J亚家族成员可将脂肪酸代谢为具有生物活性的类二十烷酸，具有很强的抗炎作用。在此，我们在96小时的lps诱导炎症和消退过程中检测了肝脏、肾脏、十二指肠和大脑中15种小鼠Cyp2c和7种小鼠Cyp2j亚型的mRNA水平。用液相色谱串联质谱法测定血浆和肝脏类二十烷酸水平。Cyp2c和Cyp2j异构体的表达变化具有异构体和组织特异性。LPS给药后24 h，肝脏总Cyp2c和Cyp2j mRNA含量降低80%，但在96 h恢复到基线水平。LPS给药后24 h，肾脏（-19%）和十二指肠（-64%）总Cyp2c和Cyp2j mRNA含量降低，但在72 h恢复到基线水平以上。LPS给药后，脑组织总Cyp2c和Cyp2j mRNA含量在所有时间点均升高。给药后3-6小时血浆类二十烷酸短暂升高。肝脏中，在急性炎症期间和恢复前，酯化氧脂水平下降。在lps诱导的炎症和消退过程中，小鼠Cyp2c和Cyp2j亚型的双相抑制和恢复以及相关的类二十烷水平变化可能具有重要的生理后果。
Inflammatory stimuli, such as bacterial LPS, alter the expression of many cytochromes P450. CYP2C and CYP2J subfamily members actively metabolize fatty acids to bioactive eicosanoids, which exhibit potent anti-inflammatory effects. Herein, we examined mRNA levels of the 15 mouse Cyp2c and 7 mouse Cyp2j isoforms in liver, kidney, duodenum, and brain over a 96-h time course of LPS-induced inflammation and resolution. Plasma and liver eicosanoid levels were also measured by liquid chromatography with tandem mass spectrometry. Expression changes in Cyp2c and Cyp2j isoforms were both isoform and tissue specific. Total liver Cyp2c and Cyp2j mRNA content was reduced by 80% 24 h after LPS but recovered to baseline levels by 96 h. Total Cyp2c and Cyp2j mRNA in kidney (-19%) and duodenum (-64%) were reduced 24 h after LPS but recovered above baseline by 72 h. Total Cyp2c and Cyp2j mRNA content in brain was elevated at all time points after LPS dosing. Plasma eicosanoids transiently increased 3-6 h after administration of LPS. In liver, esterified oxylipin levels decreased during acute inflammation and before recovering. The biphasic suppression and recovery of mouse Cyp2c and Cyp2j isoforms and associated changes in eicosanoid levels during LPS-induced inflammation and resolution may have important physiologic consequences.