Laboratory of Applied Molecular Biology and Immunology, W0414100, University of Tlemcen, 13000 Tlemcen, Algeria.
Laboratory of Applied Molecular Biology and Immunology, W0414100, University of Tlemcen, 13000 Tlemcen, Algeria; Neonatal Department of Specialized Maternal and Child Hospital of Tlemcen, 13000, Tlemcen, Algeria.
Int Immunopharmacol. 2021 Jun;95:107476. doi: 10.1016/j.intimp.2021.107476. Epub 2021 Mar 4.
Vitamin C (ascorbic acid, AscH2) has been shown to enhance immunity. Here, we studied its immunomodulatory effect on human endothelial cells (ECs) during S. aureus infection.
The ex vivo effects of AscH2 were performed on primary human umbilical vein endothelial cells (HUVECs) infected or not with S. aureus.
AscH2 treatment induced a marked downregulation of nitric oxide (NO) production and a moderate upregulation of arginase activity in S. aureus-infected HUVECs (respectively, p < 0.05 and p > 0.05). Although the upregulated release levels of soluble intercellular adhesion molecular 1 (sICAM-1/sCD54) and sE-selectin (sCD62E) molecules were not significantly different between treated and untreated S. aureus-infected HUVECs, AscH2 treatment induced reversing effect on sICAM-1 release when comparing to uninfected control HUVECs. Moreover, AscH2 treatment appears to have a significant effect on preventing HUVEC necrosis induced by S. aureus infection (p < 0.05). Furthermore, AscH2 treatment induced a significant upregulation of cell protective redox biomarker in S. aureus-infected, as shown by superoxide dismutase (SOD) activity (p < 0.05), but not by catalase activity (p > 0.05). Additionally, S. aureus infection markedly downregulated total bound calcium ions (Ca) levels as compared to control HUVECs, whereas, AscH2 treatment induced a slight upregulation of Ca levels in infected HUVECs as compared to infected and untreated HUVECs (p > 0.05). On the other hand, AscH2 treatment downregulated increased total cellular cholesterol content (CHOL) levels in HUVECs induced by S. aureus infection (p < 0.05). In addition, AscH2 treatment markedly reversed S. aureus effect on upregulation of intracellular glucose (GLU) levels within infected HUVECs (p < 0.05). Moreover, AscH2 treatment significantly downregulated S. aureus growth (p < 0.05), and significantly upregulated bacterial internalization and intracellular killing by HUVECs (p < 0.05), as well as their cell cycle activation (p < 0.01). Finally, AscH2 treatment has a slight effect on the production of interleukin 6 (IL-6), but induced a marked downregulation of that of IL-1β in S. aureus-infected HUVECs (respectively, p > 0.05, and p < 0.05).
Our outcomes demonstrated that, during S. aureus infection, AscH2 treatment promotes human ECs survival and function, as well as prevents inflammatory response exacerbation, while inducing bactericidal activity.
维生素 C（抗坏血酸，AscH2）已被证明可增强免疫力。在这里，我们研究了它在金黄色葡萄球菌感染期间对人内皮细胞（ECs）的免疫调节作用。
在体外，将 AscH2 作用于感染或未感染金黄色葡萄球菌的原代人脐静脉内皮细胞（HUVECs）上。
AscH2 处理可显著下调金黄色葡萄球菌感染的 HUVECs 中一氧化氮（NO）的产生，并适度上调精氨酸酶的活性（分别为 p<0.05 和 p>0.05）。尽管处理和未处理的金黄色葡萄球菌感染的 HUVECs 之间可溶性细胞间黏附分子 1（sICAM-1/sCD54）和可溶性 E-选择素（sE-选择素）分子的释放水平升高没有显著差异，但与未感染的对照 HUVECs 相比，AscH2 处理对 sICAM-1 的释放具有逆转作用。此外，AscH2 处理似乎对金黄色葡萄球菌感染诱导的 HUVEC 坏死具有显著的预防作用（p<0.05）。此外，AscH2 处理可诱导金黄色葡萄球菌感染的细胞保护性氧化还原生物标志物的显著上调，表现为超氧化物歧化酶（SOD）活性（p<0.05），但过氧化氢酶活性（p>0.05）没有上调。此外，与对照 HUVECs 相比，金黄色葡萄球菌感染可显著下调总结合钙离子（Ca）水平，而与感染和未处理的 HUVECs 相比，AscH2 处理可诱导感染的 HUVECs 中 Ca 水平轻微上调（p>0.05）。另一方面，AscH2 处理可下调金黄色葡萄球菌感染诱导的 HUVEC 中总细胞胆固醇（CHOL）含量的升高（p<0.05）。此外，AscH2 处理可显著逆转金黄色葡萄球菌感染对感染的 HUVEC 中细胞内葡萄糖（GLU）水平升高的影响（p<0.05）。此外，AscH2 处理可显著抑制金黄色葡萄球菌的生长（p<0.05），并显著上调 HUVECs 对内化和细胞内杀伤的作用（p<0.05），以及它们的细胞周期激活（p<0.01）。最后，AscH2 处理对白细胞介素 6（IL-6）的产生有轻微影响，但可显著下调金黄色葡萄球菌感染的 HUVECs 中白细胞介素 1β的产生（分别为 p>0.05 和 p<0.05）。
我们的研究结果表明，在金黄色葡萄球菌感染期间，AscH2 处理可促进人 ECs 的存活和功能，并防止炎症反应加重，同时诱导杀菌活性。
