Recombinant human urinary trypsin inhibitor improves the immunological function of splenic dendritic cells in mice with acute lung injury
Abstract Aim of the study 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 rep...
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BMC
2025-07-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-025-02890-z |
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| author | Tong Wang Wenna Liu Jun Li Yongli Wan Hang Su Anlong Qi |
| author_facet | Tong Wang Wenna Liu Jun Li Yongli Wan Hang Su Anlong Qi |
| author_sort | Tong Wang |
| collection | DOAJ |
| description | Abstract Aim of the study 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. Materials and methods 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. Results 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. Conclusions These results suggest that rhUTI protects LPS-induced ALI mice by improving the immune response of splenic DCs and inhibiting excessive ERS-mediated apoptosis. |
| format | Article |
| id | doaj-art-bdc5e701515e4598972b04b5ef771950 |
| institution | Kabale University |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-bdc5e701515e4598972b04b5ef7719502025-08-20T03:42:27ZengBMCEuropean Journal of Medical Research2047-783X2025-07-0130111310.1186/s40001-025-02890-zRecombinant human urinary trypsin inhibitor improves the immunological function of splenic dendritic cells in mice with acute lung injuryTong Wang0Wenna Liu1Jun Li2Yongli Wan3Hang Su4Anlong Qi5NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyNHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyNHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyNHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyNHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyDepartment of Emergency Medicine, Tianjin Medical University General HospitalAbstract Aim of the study 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. Materials and methods 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. Results 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. Conclusions These results suggest that rhUTI protects LPS-induced ALI mice by improving the immune response of splenic DCs and inhibiting excessive ERS-mediated apoptosis.https://doi.org/10.1186/s40001-025-02890-zRhUTIAcute lung injuryERS-mediated apoptosisDendritic cells |
| spellingShingle | Tong Wang Wenna Liu Jun Li Yongli Wan Hang Su Anlong Qi Recombinant human urinary trypsin inhibitor improves the immunological function of splenic dendritic cells in mice with acute lung injury European Journal of Medical Research RhUTI Acute lung injury ERS-mediated apoptosis Dendritic cells |
| title | Recombinant human urinary trypsin inhibitor improves the immunological function of splenic dendritic cells in mice with acute lung injury |
| title_full | Recombinant human urinary trypsin inhibitor improves the immunological function of splenic dendritic cells in mice with acute lung injury |
| title_fullStr | Recombinant human urinary trypsin inhibitor improves the immunological function of splenic dendritic cells in mice with acute lung injury |
| title_full_unstemmed | Recombinant human urinary trypsin inhibitor improves the immunological function of splenic dendritic cells in mice with acute lung injury |
| title_short | Recombinant human urinary trypsin inhibitor improves the immunological function of splenic dendritic cells in mice with acute lung injury |
| title_sort | recombinant human urinary trypsin inhibitor improves the immunological function of splenic dendritic cells in mice with acute lung injury |
| topic | RhUTI Acute lung injury ERS-mediated apoptosis Dendritic cells |
| url | https://doi.org/10.1186/s40001-025-02890-z |
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