Department of Emergency and Critical Care Medicine, Jinshan Hospital, Fudan University, Shanghai, 201508, China.
Department of Obstetrics and Gynecology, Jinshan Hospital, Fudan University, Shanghai, 201508, China.
Biochem Biophys Res Commun. 2020 Apr 16;524(4):876-882. doi: 10.1016/j.bbrc.2020.01.169. Epub 2020 Feb 11.
Sepsis is a progressive disease characterized by excessive inflammatory responses, severe tissue injury and organ dysfunction, ultimately leading to mortality. In this study, we demonstrated that thioredoxin-2 (TRX-2) expression is reduced in macrophages stimulated with lipopolysaccharide (LPS). Overexpression of TRX-2 significantly attenuated interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) production induced by LPS. TRX-2 inhibited LPS-induced inflammatory responses through suppressing activation of the NF-κB and MAPK signaling pathways. Furthermore, TRX-2 induced a significant decrease in mortality in mouse sepsis models in association with reduced inflammatory cytokine production and attenuation of organ injury. Our data collectively support a role of TRX-2 as a critical regulator of sepsis that influences survival by protecting the host from excessive inflammatory damage.
脓毒症是一种以过度炎症反应、严重组织损伤和器官功能障碍为特征的进行性疾病，最终导致死亡。在这项研究中，我们证明了脂多糖（LPS）刺激的巨噬细胞中硫氧还蛋白-2（TRX-2）的表达减少。TRX-2 的过表达显著减弱了 LPS 诱导的白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的产生。TRX-2 通过抑制 NF-κB 和 MAPK 信号通路的激活来抑制 LPS 诱导的炎症反应。此外，TRX-2 诱导小鼠脓毒症模型的死亡率显著降低，同时减少炎症细胞因子的产生和减轻器官损伤。我们的数据共同支持了 TRX-2 作为脓毒症的关键调节剂的作用，通过保护宿主免受过度炎症损伤来影响生存。
