Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Division of Thoracic Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
J Microbiol Immunol Infect. 2021 Jun;54(3):501-513. doi: 10.1016/j.jmii.2019.12.001. Epub 2020 Jan 25.
The regulation of the balance between inflammatory and anti-inflammatory events during the treatment of pulmonary infection is very important. Soluble Schistosoma egg antigens (SEA) can effectively inhibit the expression of cytokines during hepatic acute inflammation. However, the mechanisms by which these proteins suppress the inflammatory responses in lung cells remain unclear. The purpose of this study was to investigate the ability of SEA to inhibit pulmonary inflammation.
The effects of SEA were investigated in LPS-treated lung IMR-90 cells. The involvement of the JAK/STAT-1 signaling pathway in these effects was evaluated by employing CBA assays, quantitative polymerase chain reaction, and western blotting experiments.
Pretreatment of IMR-90 cells with appropriate concentrations of SEA protected cells against the cytotoxic effects of LPS-induced inflammation in a time-dependent manner. SEA pretreatment significantly attenuated the LPS-induced activation of the JAK/STAT1 signaling pathway, including the upregulation of JAK1/2 and STAT1, as well as the production of inflammatory cytokines. The level of phosphorylated STAT1 gradually declined in response to increasing concentrations of SEA. Based on these findings, we hypothesize that SEA-induced anti-inflammatory effects initiate with the downregulation of the IFN-γ-JAK-STAT1 signaling pathway, resulting in the attenuation of LPS-induced inflammation in IMR-90 cells.
Our study is the first to demonstrate the anti-inflammatory activity of SEA in an in vitro model of pulmonary inflammation, involving the modulation of JAK/STAT1 signaling. We propose SEA as potential therapeutic or preventive agents for the selective suppression of STAT1 and the control of inflammatory response in lung IMR-90 cells.
在肺部感染的治疗过程中，调节炎症和抗炎事件之间的平衡非常重要。可溶性血吸虫卵抗原（SEA）可有效抑制肝急性炎症期间细胞因子的表达。然而，这些蛋白抑制肺细胞炎症反应的机制尚不清楚。本研究旨在探讨 SEA 抑制肺部炎症的能力。
采用 LPS 处理的 IMR-90 细胞研究 SEA 的作用。通过 CBA 分析、定量聚合酶链反应和 Western blot 实验评估 SEA 对 JAK/STAT-1 信号通路的影响。
SEA 以时间依赖的方式预处理 IMR-90 细胞，可保护细胞免受 LPS 诱导的炎症细胞毒性作用。SEA 预处理显著减弱了 LPS 诱导的 JAK/STAT1 信号通路的激活，包括 JAK1/2 和 STAT1 的上调以及炎症细胞因子的产生。随着 SEA 浓度的增加，磷酸化 STAT1 的水平逐渐下降。基于这些发现，我们假设 SEA 诱导的抗炎作用始于 IFN-γ-JAK-STAT1 信号通路的下调，从而减弱 LPS 诱导的 IMR-90 细胞炎症。
本研究首次在体外肺炎症模型中证明了 SEA 的抗炎活性，涉及 JAK/STAT1 信号的调节。我们提出 SEA 作为一种潜在的治疗或预防药物，用于选择性抑制 STAT1 并控制肺 IMR-90 细胞的炎症反应。
