Hashida Megumi, Ranard Katherine M, Steelman Andrew J, Erdman John W
Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Department of Pediatrics, Section of Developmental Biology, University of Colorado Anschutz Medical Campus; Aurora, CO, USA.
Curr Dev Nutr. 2023 Jan 13;7(1):100017. doi: 10.1016/j.cdnut.2022.100017. eCollection 2023 Jan.
The α-tocopherol transfer protein-null () mouse model is a valuable tool for studying the molecular and functional consequences of vitamin E (α-tocopherol, αT) deficiency. Because αT has been associated with reduced oxidative stress and improved immune function, we hypothesized that depleted αT concentration would exacerbate LPS-induced acute inflammatory response in the brain and heart of mice fed a vitamin E deficient (VED) diet.
The objective was to investigate how extremely low αT status, followed by exposure to LPS, altered the acute inflammatory response to LPS in and wild-type () mice.
Three-week-old male and littermates ( = 36/genotype) ingested a VED diet ad libitum for 4 wk. At week 7, mice received an intraperitoneal LPS (1 or 10 μg/mouse) or saline (control) injection and were killed 4 h postinjection. Brain and heart IL-6 protein concentrations and tissue and serum αT concentrations were measured via ELISA and HPLC with photodiode array detection, respectively. Hippocampal , , and gene expression were measured via reverse transcriptase-quantitative polymerase chain reaction, and blood immune cell profiles were measured via a hematology analyzer.
αT accumulation in analyzed tissues and serum of mice was substantially lower than mice. Circulating white blood cell concentration, particularly lymphocytes, were lower in all LPS groups compared with controls ( < 0.01). The 10 μg LPS groups had elevated IL-6 in the cerebellum and heart compared with controls, confirming an acute inflammatory response ( < 0.01). Hippocampal and heart gene expression in the LPS-treated mice was upregulated in a dose-dependent manner ( < 0.05).
The 10 μg LPS dose enhanced inflammatory markers in the brain, heart, and serum in each genotype but the lower αT status in mice did not further impact the acute immune responses.
α-生育酚转运蛋白缺失（）小鼠模型是研究维生素E（α-生育酚，αT）缺乏的分子和功能后果的宝贵工具。由于αT与氧化应激降低和免疫功能改善有关，我们假设αT浓度降低会加剧喂食维生素E缺乏（VED）饮食的小鼠脑和心脏中脂多糖（LPS）诱导的急性炎症反应。
目的是研究极低αT状态，随后暴露于LPS，如何改变小鼠和野生型（）小鼠对LPS的急性炎症反应。
3周龄雄性小鼠和同窝小鼠（每种基因型n = 36）随意摄入VED饮食4周。在第7周，小鼠接受腹腔注射LPS（1或10μg/小鼠）或生理盐水（对照），并在注射后4小时处死。分别通过酶联免疫吸附测定（ELISA）和带光电二极管阵列检测的高效液相色谱法（HPLC）测量脑和心脏白细胞介素-6（IL-6）蛋白浓度以及组织和血清αT浓度。通过逆转录定量聚合酶链反应测量海马、和基因表达，并通过血液分析仪测量血液免疫细胞谱。
小鼠分析组织和血清中的αT积累明显低于小鼠。与对照组相比，所有LPS组的循环白细胞浓度，特别是淋巴细胞浓度较低（P < 0.01）。与对照组相比，10μg LPS组小脑和心脏中的IL-6升高，证实存在急性炎症反应（P < 0.01）。LPS处理的小鼠海马和心脏基因表达以剂量依赖性方式上调（P < 0.05）。
10μg LPS剂量增强了每种基因型脑、心脏和血清中的炎症标志物，但小鼠中较低的αT状态并未进一步影响急性免疫反应。
