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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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
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| Series: | European Journal of Medical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40001-025-02890-z |
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| Summary: | 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. |
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| ISSN: | 2047-783X |