Guo Pu, Liu Xuwen, Li Xiaoyi, Ihsan Awais, Wu Zhongyuan, Fu Shulin, Ye Chun, Qiu Yinsheng, Wang Xu, Lu Qirong, Liu Yu
Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China.
Wuhan Engineering and Technology Research Center of Animal Disease-Resistant Nutrition, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China.
Antibiotics (Basel). 2025 Aug 12;14(8):824. doi: 10.3390/antibiotics14080824.
(GPS) is a conditional pathogen that colonizes the upper respiratory tract in pigs and causes Glässer's disease, resulting in high morbidity and mortality in piglets. GPS infection increases the vascular endothelial permeability, but the mechanism has not been fully elucidated. Luteolin (Lut) is a naturally occurring flavonoid found in plants such as vegetables, herbs, and fruits, but its potential to treat the increased vascular endothelial permeability caused by GPS infection has not been evaluated. This study revealed that GPS infection induces increased vascular endothelial permeability in porcine iliac artery endothelial cells (PIECs) by increasing the gene expressions of tumor necrosis factor (TNF), interleukin 6 (IL-6), IL-8, and IL-1β, and by regulating F-actin cytoskeleton reorganization. Mechanistically, GPS infection or Cluster of differentiation 44 (CD44) overexpression significantly increased the expressions of vascular-endothelial-permeability-related proteins (CD44; vascular endothelial growth factor (VEGFA); matrixmetalloProteinase-3 (MMP-3); MMP-9; and SRC proto-oncogene, non-receptor tyrosine kinase (c-Src)) and increased the vascular endothelial permeability; these changes were alleviated by a Lut treatment or CD44 silencing in the PIECs. This study comprehensively illustrates the potential targets and molecular mechanism of Lut in alleviating the GPS-induced increase in vascular endothelial permeability. The CD44 pathway and Lut may be an effective target and antibiotic alternative, respectively, to prevent the increased vascular endothelial permeability caused by GPS.
猪肺炎支原体（GPS）是一种条件性病原菌，可定殖于猪的上呼吸道并引发猪传染性胸膜肺炎，导致仔猪高发病率和死亡率。GPS感染会增加血管内皮通透性，但其机制尚未完全阐明。木犀草素（Lut）是一种天然存在的黄酮类化合物，存在于蔬菜、草药和水果等植物中，但其治疗GPS感染引起的血管内皮通透性增加的潜力尚未得到评估。本研究表明，GPS感染通过增加肿瘤坏死因子（TNF）、白细胞介素6（IL-6）、IL-8和IL-1β的基因表达以及调节F-肌动蛋白细胞骨架重组，诱导猪髂动脉内皮细胞（PIECs）的血管内皮通透性增加。机制上，GPS感染或分化簇44（CD44）过表达显著增加了血管内皮通透性相关蛋白（CD44；血管内皮生长因子（VEGFA）；基质金属蛋白酶-3（MMP-3）；MMP-9；以及SRC原癌基因、非受体酪氨酸激酶（c-Src））的表达，并增加了血管内皮通透性；PIECs中的Lut处理或CD44沉默可缓解这些变化。本研究全面阐明了Lut在减轻GPS诱导的血管内皮通透性增加方面的潜在靶点和分子机制。CD44途径和Lut可能分别是预防GPS引起的血管内皮通透性增加的有效靶点和抗生素替代品。
