Sepsis is a disease that is characterized by a severe systemic inflammatory response to microbial infection and lipopolysaccharide (LPS) and is a well-known inducer of sepsis, as well as endothelial cell hyperpermeability. In the present study, we confirm the elevation of CXC chemokine ligand 13 (CXCL13) in sepsis patients. We also show that LPS exposure increases the release of CXCL13, as well as the mRNA and protein expression of CXCL13 and its receptor, CXC chemokine receptor 5 (CXCR5) in human umbilical vein endothelial cells (HUVECs) in a dose- and time-dependent manner. We also examined the effects of CXCL13 knockdown on LPS-mediated endothelial hyperpermeability and tight junction (TJ) protein expression in HUVECs. Our results show that HUVECs exposed to LPS result in a significant decrease in transendothelial electrical resistance (TER) and TJ protein (Zonula occluden-1, occludin, and claudin-4) expression, and a notable increase in fluorescein isothiocyanate (FITC)-dextran flux and p38 phosphorylation, which was partially reversed by CXCL13 knockdown. Recombinant CXCL13 treatment had a similar effect as LPS exposure, which was attenuated by a p38 inhibitor, SB203580. Moreover, the CXCL13-neutralizing antibody significantly increased the survival rate of LPS-induced sepsis mice. Collectively, our results show that CXCL13 plays a key role in LPS-induced endothelium hyperpermeability via regulating p38 signaling and suggests that therapeutically targeting CXCL13 may be beneficial for the treatment of sepsis.

脓毒症是一种疾病，其特征在于对微生物感染和脂多糖（LPS）的严重全身性炎症反应，并且是脓毒症以及内皮细胞通透性过高的众所周知的诱导剂。在本研究中，我们确认败血症患者中CXC趋化因子配体13（CXCL13）的升高。我们还显示，LPS暴露会在人脐静脉内皮细胞（HUVEC）中增加CXCL13的释放以及CXCL13及其受体CXC趋化因子受体5（CXCR5）的mRNA和蛋白表达，并呈剂量和时间依赖性。方式。我们还检查了CXCL13敲低对HUVEC中LPS介导的内皮细胞通透性和紧密连接（TJ）蛋白表达的影响。我们的结果表明，暴露于LPS的HUVEC导致内皮电阻（TER）和TJ蛋白（Zonula occluden-1，occludin和claudin-4）表达显着降低，异硫氰酸荧光素（FITC）-右旋糖酐显着增加通量和p38磷酸化，这被CXCL13敲低部分逆转。重组CXCL13处理的效果与LPS暴露相似，但被p38抑制剂SB203580减弱。此外，CXCL13中和抗体显着提高了LPS诱导的败血症小鼠的存活率。总的来说，我们的结果表明CXCL13在LPS诱导的内皮通透性过高中起关键作用 这被CXCL13组合所部分逆转。重组CXCL13处理的效果与LPS暴露相似，但被p38抑制剂SB203580减弱。此外，CXCL13中和抗体显着提高了LPS诱导的败血症小鼠的存活率。总的来说，我们的结果表明CXCL13在LPS诱导的内皮通透性过高中起关键作用 这被CXCL13组合所部分逆转。重组CXCL13处理的效果与LPS暴露相似，但被p38抑制剂SB203580减弱。此外，CXCL13中和抗体显着提高了LPS诱导的败血症小鼠的存活率。总的来说，我们的结果表明CXCL13在LPS诱导的内皮通透性过高中起关键作用通过调节p38信号转导，提示治疗性靶向CXCL13可能对败血症的治疗有益。