Wang Tong, Liu Wenna, Li Jun, Wan Yongli, Su Hang, Qi Anlong
NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin, 300134, China.
Department of Emergency Medicine, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin, 300052, China.
Eur J Med Res. 2025 Jul 9;30(1):604. doi: 10.1186/s40001-025-02890-z.
Acute lung injury (ALI) is a common critical condition in the emergency department and is associated with a high mortality rate. Recombinant human urinary trypsin inhibitor (rhUTI), a serine protease inhibitor compounded by genetic engineering technology, is expected to replace UTI, which has been reported to protect multiple organs against inflammation- and/or injury-induced dysfunction. The aim of the present study was to investigate the immunomodulatory effects of rhUTI on splenic dendritic cells (DCs) in LPS-induced ALI mice.
RhUTI was administered to mice, and splenic CD11c + DCs were isolated and assessed using flow cytometry for apoptotic or phenotypic analysis. Protein markers and cytokines were determined by western blotting or enzyme-linked immunosorbent assay.
After treatment with rhUTI, lung injury in LPS-induced ALI mice improved and the survival rate of the mice increased. Treatment with rhUTI could markedly upregulate the levels of co-stimulatory molecules (CD80 and CD86) and major histocompatibility complex class II molecules (MHC-II) on the surface of splenic DC and decreased the apoptosis rate of splenic DCs in LPS-induced ALI mice. In addition, protein levels of markers of endoplasmic reticulum stress (ERS) and ERS-related apoptotic pathways (including GRP78, XBP-1, PERK, caspase-12, and CHOP) were downregulated in the rhUTI-treated group when compared with the LPS-induced ALI group.
These results suggest that rhUTI protects LPS-induced ALI mice by improving the immune response of splenic DCs and inhibiting excessive ERS-mediated apoptosis.
急性肺损伤（ALI）是急诊科常见的危急病症，死亡率高。重组人尿胰蛋白酶抑制剂（rhUTI）是一种采用基因工程技术合成的丝氨酸蛋白酶抑制剂，有望取代尿胰蛋白酶抑制剂（UTI），据报道UTI可保护多个器官免受炎症和/或损伤诱导的功能障碍。本研究的目的是探讨rhUTI对脂多糖（LPS）诱导的ALI小鼠脾脏树突状细胞（DCs）的免疫调节作用。
给小鼠注射rhUTI，分离脾脏CD11c + DCs，采用流式细胞术进行凋亡或表型分析。通过蛋白质印迹法或酶联免疫吸附测定法测定蛋白质标志物和细胞因子。
rhUTI治疗后，LPS诱导的ALI小鼠肺损伤改善，小鼠存活率提高。rhUTI治疗可显著上调LPS诱导的ALI小鼠脾脏DC表面共刺激分子（CD80和CD86）和主要组织相容性复合体II类分子（MHC-II）的水平，并降低脾脏DC的凋亡率。此外，与LPS诱导的ALI组相比，rhUTI治疗组内质网应激（ERS）和ERS相关凋亡途径（包括GRP78、XBP-1、PERK、caspase-12和CHOP）的标志物蛋白水平下调。
这些结果表明，rhUTI通过改善脾脏DC的免疫反应和抑制过度的ERS介导的凋亡来保护LPS诱导的ALI小鼠。
