Tripterygium wilfordii attenuates acute lung injury by regulating the differentiation and function of myeloid-derived suppressor cells.
10.11817/j.issn.1672-7347.2025.240424
- Author:
Lingyu WEI
1
,
2
,
3
;
Shu TONG
4
;
Meng'er WANG
4
;
Hongzheng REN
4
;
Jinsheng WANG
3
,
5
,
6
Author Information
1. Clinical Research Center Laboratory, Heping Hospital Affiliated to Changzhi Medical College, Changzhi
2. weilingyu0425@
3. com.
4. Department of Pathology, Heping Hospital Affiliated to Changzhi Medical College, Changzhi
5. Department of Pathology, First Clinical College, Changzhi Medical College, Changzhi
6. wjsczmc@
- Publication Type:Journal Article
- Keywords:
Tripterygium wilfordii;
acute lung injury;
arginase-1;
myeloid-derived suppressor cells;
reactive oxygen species
- MeSH:
Animals;
Acute Lung Injury/chemically induced*;
Myeloid-Derived Suppressor Cells/cytology*;
Tripterygium/chemistry*;
Mice, Inbred C57BL;
Mice;
Cell Differentiation/drug effects*;
Male;
Lipopolysaccharides;
Nitric Oxide Synthase Type II/genetics*;
Cytokines/metabolism*;
Reactive Oxygen Species/metabolism*;
Diterpenes/pharmacology*;
Epoxy Compounds;
Phenanthrenes
- From:
Journal of Central South University(Medical Sciences)
2025;50(5):840-850
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES:Acute lung injury (ALI) is an acute respiratory failure syndrome characterized by impaired gas exchange. Due to the lack of effective targeted drugs, it is associated with high mortality and poor prognosis. Tripterygium wilfordii (TW) has demonstrated anti-inflammatory activity in the treatment of various diseases. This study aims to investigate the effects and underlying mechanisms of TW on myeloid-derived suppressor cells (MDSCs) in ALI, providing experimental evidence for TW as a potential adjuvant therapy for ALI.
METHODS:Eighteen specific pathogen-free (SPF) C57BL/6 mice were randomly divided into normal control (NC; intranasal saline), lipopolysaccharide (LPS; 5 mg/kg intranasally to induce ALI), and LPS+TW (50 mg/kg TW by gavage on the first day of modeling, followed by 5 mg/kg LPS intranasally to induce ALI) groups (n=6 each). Lung injury and edema were assessed by histopathological scoring and wet-to-dry weight ratio. Cytokine levels [interleukin (IL)-1β, IL-6, IL-18, tumor necrosis factor-α (TNF-α)] in lung tissue lavage fluid were measured by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to assess the proportions of MDSCs, polymorphonuclear MDSCs (PMN-MDSCs), and monocytic MDSCs (M-MDSCs) in bone marrow, spleen, peripheral blood, and lung tissue, as well as reactive oxygen species (ROS) levels in lung tissues. Messenger RNA (mRNA) expression levels of inducible nitric oxide synthase (iNOS) and arginase-1 (ARG-1) in lung tissues were determined by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). PMN-MDSCs sorted from the lungs of LPS-treated mice were co-cultured with splenic CD3+ T cells and divided into NC, triptolide (TPL)-L, and TPL-H groups, with bovine serum albumin, 25 nmol/L TPL, and 50 nmol/L TPL, respectively. Flow cytometry was used to detect the effect of PMN-MDSCs on T-cell proliferation, and RT-qPCR was used to measure iNOS and ARG-1 mRNA expression.
RESULTS:Compared with the NC group, the LPS group showed marked lung pathology with significantly increased histopathological scores and wet-to-dry ratios (both P<0.001). TW treatment significantly alleviated lung injury and reduced both indices compared with the LPS group (both P<0.05). Cytokine levels were significantly decreased in the LPS+TW group compared with the LPS group (all P<0.001). The proportions of MDSCs in CD45+ cells from spleen, bone marrow, peripheral blood, and lung, as well as PMN-MDSCs from spleen, peripheral blood, and lung, were significantly reduced in the LPS+TW group compared with the LPS group (all P<0.05), accompanied by reduced ROS levels in lung tissues (P<0.001). iNOS and ARG-1 mRNA expression in lung tissues was significantly lower in the LPS+TW group than in the LPS group (both P<0.001). In vitro, compared with the TPL-L group, the TPL-H group showed significantly increased CD3+ T-cell proliferation (P<0.001), and decreased iNOS and ARG-1 mRNA expression (all P<0.05).
CONCLUSIONS:TW alleviates the progression of LPS-induced ALI in mice, potentially by reducing the proportion of MDSCs in lung tissues and attenuating the immunosuppressive function of PMN-MDSCs.
