Department of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Int Immunopharmacol. 2021 Feb;91:107295. doi: 10.1016/j.intimp.2020.107295. Epub 2020 Dec 21.
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a severe form of inflammatory lung disease. Its development and progression are regulated by cytokines. The purpose of this study was to determine the effects of HMGB1 involved in the regulation of Treg cells and IL-35.
A cecal ligation and puncture (CLP)-induced ALI model was used to investigate the changes in IL-35, Tregs, and the expression of RAGE and caspase-11 after HMGB1 inhibition (glycyrrhizin was used as an inhibitor of HMGB1). CD4+ naïve T cells sorted from C57BL/6 mice spleens were cultured to explore the role of HMGB1 in the differentiation from CD4+ naïve T cells to Tregs.
HMGB1 promoted lung injury and uncontrolled inflammation in the CLP mouse model. HMGB1, NF-κB p65, RAGE, and caspase-11 expression in the lungs of CLP mice decreased significantly after pretreatment with glycyrrhizin. We found that the Treg proportion and IL-35 expression were upregulated in the serum and lung of CLP mice after inhibiting HMGB1. In our in vitro experiments, we found that recombinant HMGB1 significantly suppressed the proportion of CD4+CD25+FOXP3+Tregs differentiated from CD4+ naïve T cells.
The inhibition of HMGB1 increased the proportion of Treg and expression of IL-35 and alleviated lung injury in the CLP-induced ALI model. Furthermore, inhibition of HMGB1 reduced caspase-11-dependent pyroptosis in the lungs of the CLP-induced ALI model.
急性肺损伤/急性呼吸窘迫综合征（ALI/ARDS）是一种严重的炎症性肺疾病。其发生发展受细胞因子调控。本研究旨在探讨高迁移率族蛋白 B1（HMGB1）调控调节性 T 细胞（Treg）及白细胞介素-35（IL-35）的作用。
采用盲肠结扎穿孔（CLP）诱导的 ALI 模型，观察 HMGB1 抑制（甘草甜素作为 HMGB1 抑制剂）后 IL-35、Treg 及 RAGE、caspase-11 的变化。从小鼠脾脏分离 CD4+naive T 细胞，体外培养，观察 HMGB1 对 CD4+naive T 细胞向 Treg 分化的作用。
HMGB1 促进 CLP 小鼠模型的肺损伤和失控性炎症。CLP 小鼠肺组织中 HMGB1、NF-κB p65、RAGE、caspase-11 表达经甘草甜素预处理后明显下降。我们发现抑制 HMGB1 后 CLP 小鼠血清和肺组织中 Treg 比例及 IL-35 表达上调。在体外实验中，我们发现重组 HMGB1 明显抑制 CD4+naive T 细胞向 CD4+CD25+FOXP3+Treg 分化的比例。
HMGB1 抑制可增加 Treg 比例和 IL-35 表达，减轻 CLP 诱导的 ALI 模型中的肺损伤。此外，HMGB1 抑制可减少 CLP 诱导的 ALI 模型中 caspase-11 依赖性细胞焦亡。
