Department of Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Neonatology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Immunol. 2020 Oct 15;11:534099. doi: 10.3389/fimmu.2020.534099. eCollection 2020.
Interleukin (IL)-33 is a member of the IL-1 family, which plays an important role in inflammatory response. In this study, we evaluated the effect of IL-33 on septicemia and the underlying mechanisms by establishing a ()-induced septicemic mouse model. The expression of IL-33, IL-1α, IL-1β, IL-6, IL-17A, IL-22, and PGE2 were measured by double antibody sandwich enzyme-linked immunosorbent assay, and bacterial colony formation in peripheral blood and kidneys were counted postinfection. The percentages of neutrophils, eosinophils, and inflammatory monocytes were evaluated by flow cytometry, and tissue damage was assessed by hematoxylin and eosin (H&E) staining. The survival of septicemic mice was monitored daily. IL-33 expression was significantly augmented following infection. High IL-33 expression significantly decreased the survival of model mice, and aggravated the damage of lung, liver, and kidney tissues. However, administration of ST2 (receptor for IL-33) to the -infected mice blocked the IL-33 signaling pathway, which elevated PGE2, IL-17A, and IL-22, and promoted healing of organ damage. In addition, ST2 suppressed the mobilization of inflammatory monocytes, but promoted the accumulation of neutrophils and eosinophils in -infected mice. Inhibition of PGE2, IL-17A, and IL-22 facilitated the development of septicemia and organ damage in -infected mice, as well as reducing their survival. Our findings reveal that IL-33 aggravates organ damage in septicemic mice by inhibiting PGE2, IL-17A, and IL-22 production.
白细胞介素 (IL)-33 是 IL-1 家族的成员，在炎症反应中发挥重要作用。在本研究中，我们通过建立（）诱导的败血症小鼠模型来评估 IL-33 对败血症的影响及其潜在机制。通过双抗体夹心酶联免疫吸附试验测量 IL-33、IL-1α、IL-1β、IL-6、IL-17A、IL-22 和 PGE2 的表达，并在感染后计数外周血和肾脏中的细菌菌落形成。通过流式细胞术评估中性粒细胞、嗜酸性粒细胞和炎症性单核细胞的百分比，并通过苏木精和伊红 (H&E) 染色评估组织损伤。每天监测败血症小鼠的存活情况。感染后 IL-33 的表达明显增加。高表达 IL-33 显著降低模型小鼠的存活率，并加重肺、肝和肾组织的损伤。然而，向感染的小鼠施用 ST2（IL-33 的受体）阻断了 IL-33 信号通路，从而升高了 PGE2、IL-17A 和 IL-22，并促进了器官损伤的愈合。此外，ST2 抑制了炎症性单核细胞的动员，但促进了感染小鼠中性粒细胞和嗜酸性粒细胞的积累。抑制 PGE2、IL-17A 和 IL-22 促进了感染的小鼠败血症和器官损伤的发展，并降低了它们的存活率。我们的研究结果表明，IL-33 通过抑制 PGE2、IL-17A 和 IL-22 的产生来加重败血症小鼠的器官损伤。
