Jooyeon Lee, Jimin Jang, Sang-Ryul Cha, Se Bi Lee, Seok-Ho Hong, Han-Sol Bae, Young Jin Lee, Se-Ran Yang
{"title":"Recombinant Human Bone Morphogenetic Protein-2 Priming of Mesenchymal Stem Cells Ameliorate Acute Lung Injury by Inducing Regulatory T Cells.","authors":"Jooyeon Lee, Jimin Jang, Sang-Ryul Cha, Se Bi Lee, Seok-Ho Hong, Han-Sol Bae, Young Jin Lee, Se-Ran Yang","doi":"10.4110/in.2023.23.e48","DOIUrl":null,"url":null,"abstract":"<p><p>Mesenchymal stromal/stem cells (MSCs) possess immunoregulatory properties and their regulatory functions represent a potential therapy for acute lung injury (ALI). However, uncertainties remain with respect to defining MSCs-derived immunomodulatory pathways. Therefore, this study aimed to investigate the mechanism underlying the enhanced effect of human recombinant bone morphogenic protein-2 (rhBMP-2) primed ES-MSCs (MSC<sup>BMP2</sup>) in promoting Tregs in ALI mice. MSC were preconditioned with 100 ng/ml rhBMP-2 for 24 h, and then administrated to mice by intravenous injection after intratracheal injection of 1 mg/kg LPS. Treating MSCs with rhBMP-2 significantly increased cellular proliferation and migration, and cytokines array reveled that cytokines release by MSC<sup>BMP2</sup> were associated with migration and growth. MSC<sup>BMP2</sup> ameliorated LPS induced lung injury and reduced myeloperoxidase activity and permeability in mice exposed to LPS. Levels of inducible nitric oxide synthase were decreased while levels of total glutathione and superoxide dismutase activity were further increased via inhibition of phosphorylated STAT1 in ALI mice treated with MSC<sup>BMP2</sup>. MSC<sup>BMP2</sup> treatment increased the protein level of IDO1, indicating an increase in Treg cells, and Foxp3<sup>+</sup>CD25<sup>+</sup> Treg of CD4<sup>+</sup> cells were further increased in ALI mice treated with MSC<sup>BMP2</sup>. In co-culture assays with MSCs and RAW264.7 cells, the protein level of IDO1 was further induced in MSC<sup>BMP2</sup>. Additionally, cytokine release of IL-10 was enhanced while both IL-6 and TNF-α were further inhibited. In conclusion, these findings suggest that MSC<sup>BMP2</sup> has therapeutic potential to reduce massive inflammation of respiratory diseases by promoting Treg cells.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10767548/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immune Network","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4110/in.2023.23.e48","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/12/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Mesenchymal stromal/stem cells (MSCs) possess immunoregulatory properties and their regulatory functions represent a potential therapy for acute lung injury (ALI). However, uncertainties remain with respect to defining MSCs-derived immunomodulatory pathways. Therefore, this study aimed to investigate the mechanism underlying the enhanced effect of human recombinant bone morphogenic protein-2 (rhBMP-2) primed ES-MSCs (MSCBMP2) in promoting Tregs in ALI mice. MSC were preconditioned with 100 ng/ml rhBMP-2 for 24 h, and then administrated to mice by intravenous injection after intratracheal injection of 1 mg/kg LPS. Treating MSCs with rhBMP-2 significantly increased cellular proliferation and migration, and cytokines array reveled that cytokines release by MSCBMP2 were associated with migration and growth. MSCBMP2 ameliorated LPS induced lung injury and reduced myeloperoxidase activity and permeability in mice exposed to LPS. Levels of inducible nitric oxide synthase were decreased while levels of total glutathione and superoxide dismutase activity were further increased via inhibition of phosphorylated STAT1 in ALI mice treated with MSCBMP2. MSCBMP2 treatment increased the protein level of IDO1, indicating an increase in Treg cells, and Foxp3+CD25+ Treg of CD4+ cells were further increased in ALI mice treated with MSCBMP2. In co-culture assays with MSCs and RAW264.7 cells, the protein level of IDO1 was further induced in MSCBMP2. Additionally, cytokine release of IL-10 was enhanced while both IL-6 and TNF-α were further inhibited. In conclusion, these findings suggest that MSCBMP2 has therapeutic potential to reduce massive inflammation of respiratory diseases by promoting Treg cells.
期刊介绍:
Immune Network publishes novel findings in basic and clinical immunology and aims to provide a medium through which researchers in various fields of immunology can share and connect. The journal focuses on advances and insights into the regulation of the immune system and the immunological mechanisms of various diseases. Research that provides integrated insights into translational immunology is given preference for publication. All submissions are evaluated based on originality, quality, clarity, and brevity