Trauma Research Center, Fourth Medical Center and Medical Innovation Research Department of the Chinese PLA General Hospital, Beijing 100048, People's Republic of China; Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin 300052, People's Republic of China.
Trauma Research Center, Fourth Medical Center and Medical Innovation Research Department of the Chinese PLA General Hospital, Beijing 100048, People's Republic of China.
Int Immunopharmacol. 2020 Aug;85:106643. doi: 10.1016/j.intimp.2020.106643. Epub 2020 May 27.
Urinary trypsin inhibitor (UTI), also known as ulinastatin, has been reported to protect multiple organs against inflammation- and/or injury-induced dysfunction. In the present study, we aimed to investigate the immunomodulation effects of a recombinant human ulinastatin (urinary trypsin inhibitor, UTI) (rhUTI) on splenic dendritic cells (DCs) in cecal ligation and puncture (CLP)-induced septic mice. CLP mice were treated with rhUTI intramuscularly at 0, 12, and 24 h after procedure. Splenic CD11c DCs were isolated and accessed with flow cytometry for apoptotic or phenotypic analysis. Protein markers and cytokines were determined with Western blotting or ELISA. Treatment with rhUTI could markedly upregulate levels of costimulatory molecules (CD80, CD86) and MHC-II on surface of the splenic DC in CLP mice. The apoptotic rate of splenic DCs was decreased in CLP mice after rhUTI treatment. The survival rate of septic mice was increased after treatment with rhUTI. In addition, protein level of markers in endoplasmic reticulum stress (ERS)-related apoptotic pathways (including GRP78, caspase-12, and CHOP) were obviously down-regulated in the rhUTI-treated group when compared with the CLP group. These results indicate that rhUTI protects CLP-induced sepsis in mice by improving immune response of splenic DCs and inhibiting the excessive ERS-mediated apoptosis.
尿胰蛋白酶抑制剂（UTI），也称为乌司他丁，已被报道可保护多种器官免受炎症和/或损伤引起的功能障碍。在本研究中，我们旨在研究重组人乌司他丁（rhUTI）对盲肠结扎和穿刺（CLP）诱导的脓毒症小鼠脾脏树突状细胞（DC）的免疫调节作用。CLP 小鼠在手术后 0、12 和 24 小时肌肉内给予 rhUTI 治疗。分离脾 CD11c DC，用流式细胞术检测凋亡或表型分析。用 Western blot 或 ELISA 测定蛋白标志物和细胞因子。rhUTI 处理可显著上调 CLP 小鼠脾 DC 表面共刺激分子（CD80、CD86）和 MHC-II 的水平。rhUTI 处理可降低 CLP 小鼠脾 DC 的凋亡率。rhUTI 治疗可提高脓毒症小鼠的存活率。此外，与 CLP 组相比，rhUTI 治疗组内质网应激（ERS）相关凋亡途径（包括 GRP78、caspase-12 和 CHOP）的标志物蛋白水平明显下调。这些结果表明，rhUTI 通过改善脾 DC 的免疫反应和抑制过度的 ERS 介导的凋亡来保护 CLP 诱导的脓毒症小鼠。
