β-羟基丁酸损害酮病奶牛的单核细胞功能及活性氧-含NLR家族吡啶结构域3炎性小体（NLRP3）途径。
β-hydroxybutyrate impairs monocyte function the ROS-NLR family pyrin domain-containing three inflammasome (NLRP3) pathway in ketotic cows.
作者信息
Dong Zhihao, Sun Xudong, Tang Yan, Luo Shengbin, Jia Hongdou, Xu Qiushi, Jiang Qianming, Loor Juan J, Xu Wei, Xu Chuang
机构信息
Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China.
Mammalian NutriPhysioGenomics, Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana, IL, United States.
出版信息
Front Vet Sci. 2022 Aug 29;9:925900. doi: 10.3389/fvets.2022.925900. eCollection 2022.
Cows with ketosis display severe metabolic stress and immune dysfunction which renders them more susceptible to infections. Monocytes, one of the major subtypes of white blood cells, play an important role in innate immune defense against infections. Thus, the aim of this study was to investigate alterations in immune function, reactive oxygen species (ROS) production and activity of the NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway in monocytes (CD14) of cows with clinical ketosis (CK). Twelve healthy multiparous Holstein cows [blood β-hydroxybutyrate (BHB) concentration < 1.2 m] and 12 cows with CK (BHB > 3.0 m) at 3 to 14 days in milk were used for blood sample collection. To determine effects of BHB on phagocytosis, ROS and protein abundance of the NLRP3 inflammasome pathway , monocytes isolated from healthy cows were treated with 3.0 m BHB for 0, 6, 12 or 24 h. Dry matter intake (22.7 vs. 19.0 kg) was lower in cows with CK. Serum concentrations of fatty acids (0.30 vs. 0.88 m) and BHB (0.52 vs. 3.78 m) were greater in cows with CK, whereas concentration of glucose was lower (4.09 vs. 2.23 m). The adhesion, migration and phagocytosis of monocytes were lower in cows with CK, but apoptosis and ROS content were greater. Protein abundance of NLRP3, cysteinyl aspartate specific proteinase 1 (caspase 1) and interleukin-1B p17 (IL1B p17) were greater in monocytes of cows with CK, while abundance of NADPH oxidase isoform 2 (NOX2) was lower. Compared with 0 h BHB, ROS content and apoptosis were greater in the monocytes challenged for 6, 12 or 24 h BHB. Compared with 0 h BHB, protein abundance of NLRP3, caspase 1, IL1B p17 and concentration of IL1B in medium were greater in the monocytes challenged for 6, 12 or 24 h BHB. However, compared with 0 h BHB, protein abundance of NOX2 and phagocytosis of monocytes were lower in the monocytes challenged for 6, 12 or 24 h BHB. Overall, the data suggested that exogenous BHB activated the ROS-NLRP3 pathway, which might be partly responsible for immune dysfunction of dairy cows with CK.
患有酮病的奶牛表现出严重的代谢应激和免疫功能障碍，这使它们更容易受到感染。单核细胞是白细胞的主要亚型之一，在针对感染的固有免疫防御中发挥重要作用。因此，本研究的目的是调查临床酮病（CK）奶牛单核细胞（CD14）中免疫功能、活性氧（ROS）产生以及含NLR家族pyrin结构域3（NLRP3）炎性小体途径的活性变化。选取12头健康经产荷斯坦奶牛[血液β-羟基丁酸（BHB）浓度<1.2 mmol/L]和12头处于产奶3至14天的CK奶牛（BHB>3.0 mmol/L）进行血样采集。为了确定BHB对吞噬作用、ROS以及NLRP3炎性小体途径蛋白丰度的影响，将从健康奶牛分离出的单核细胞用3.0 mmol/L BHB处理0、6、12或24小时。CK奶牛的干物质摄入量较低（22.7对19.0千克）。CK奶牛的血清脂肪酸浓度（0.30对0.88 mmol/L）和BHB浓度（0.52对3.78 mmol/L）较高，而葡萄糖浓度较低（4.09对2.23 mmol/L）。CK奶牛单核细胞的黏附、迁移和吞噬作用较低，但凋亡和ROS含量较高。CK奶牛单核细胞中NLRP3、半胱天冬酶1（caspase 1）和白细胞介素-1β p17（IL1B p17）的蛋白丰度较高，而烟酰胺腺嘌呤二核苷酸磷酸氧化酶同工型2（NOX2）的丰度较低。与0小时BHB处理相比，用BHB处理6、12或24小时的单核细胞中ROS含量和凋亡更高。与0小时BHB处理相比，用BHB处理6、12或24小时的单核细胞中NLRP3、caspase 1、IL1B p17的蛋白丰度以及培养基中IL1B的浓度更高。然而，与0小时BHB处理相比，用BHB处理6、12或24小时的单核细胞中NOX2的蛋白丰度和单核细胞的吞噬作用更低。总体而言，数据表明外源性BHB激活了ROS-NLRP3途径，这可能部分导致了CK奶牛的免疫功能障碍。
Zotero 插件