Bone marrow mesenchymal stem cells attenuate LPS-induced acute lung injury in mice by promoting RvE1/ProD1 and modulating Treg/Th17 balance

He-Bu Qian; Guijuan Zou; Chao Li; Qi-Fang He; Jun Liu

doi:10.3906/biy-2107-83

Bone marrow mesenchymal stem cells attenuate LPS-induced acute lung injury in mice by promoting RvE1/ProD1 and modulating Treg/Th17 balance

Turk J Biol. 2021 Dec 20;46(2):173-185. doi: 10.3906/biy-2107-83. eCollection 2022.

Authors

He-Bu Qian^#¹, Guijuan Zou^#², Chao Li², Qi-Fang He², Jun Liu²

Affiliations

¹ Department of Critical Care Medicine, Suzhou Ninth People's Hospital, The Affiliated Wujiang Hospital of Nantong University, Suzhou, China.
² Gusu School of Nanjing Medical University, Department of Critical Care Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou Clinical Medical Center of Critical Care Medicine, Suzhou, China.

^# Contributed equally.

Abstract

Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are respiratory failures caused by excessive alveolar inflammation with high mortality. In this study, we investigated the effects of bone marrow mesenchymal stem cells (BMSCs) on lung injury of lipopolysaccharide (LPS)-induced ALI and explored the associated mechanisms. BMSCs were isolated, cultured, identified by staining with CD34 and CD44 surface markers. LPS-induced ALI mouse model was generated by injecting with LPS and divided into ALI group and ALI+BMSCs group. Mice treated without any reagents were assigned as Control, mice transplanted with BMSCs were assigned as BMSCs group. Regulatory T (Treg) and Th17 percentages were evaluated using flow cytometry. Proresolving mediators (resolvin E1 (RvE1), protectin D1 (ProD1)) in lung tissue and cytokines (interleukin-6 (IL-6) and IL-17) in serum were analyzed by ELISA. Myeloperoxidase (MPO) activity was determined. Cultured cells demonstrated typical characteristics of BMSCs. BMSCs transplantation (ALI+BMSCs) obviously alleviated LPS-induced ALI in mice. BMSCs transplantation significantly decreased MPO activity in LPS-induced ALI in mice compared to the Control group (p < 0.05). BMSCs transplantation markedly increased Treg percentages and decreased dendritic cells (DCs) and Th17 cells percentages compared to those of the Control group (p < 0.05). BMSCs transplantation remarkably enhanced RvE1 and ProD1 levels in LPS-induced ALI (ALI+BMSCs) compared to the ALI group (p < 0.05). BMSCs transplantation significantly attenuated IL-6 and IL-17 levels in serum of mice treated with LPS (ALI+BMSCs) compared to those of the ALI group (p < 0.05). In conclusion, BMSCs transplantation effectively attenuated LPS-induced pathological injury of ALI in mice, at least partly through promoting proresolving mediators RvE1 and ProD1 and modulating the balance of Treg/Th17.

Keywords: Acute lung injury; Th17 cells; Treg; acute respiratory distress syndrome; mesenchymal stem cells; proresolving mediators.

Grants and funding

This study was supported by the Scientific and Technological Development Project of Suzhou (SS201874), Scientific Project of Gusu School, Nanjing Medical University (GSKY20210225), Key Social Development Project of Jiangsu Province, Project of Cardiovascular Multidisciplinary Integrated Thinking of China Foundation for International Medical Exchange (Z-2016-23-2101-23) and Key Social Development Project of Jiangsu Province (BE2021660).