Luteolin Regulates the Differentiation of Regulatory T Cells and Activates IL-10-Dependent Macrophage Polarization against Acute Lung Injury
Objectives. Inflammatory disease characterized by clinical destructive respiratory disorder is called acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Studies have shown that luteolin exerts anti-inflammatory effects by increasing regulatory T cells (Tregs). In this study, we aimed...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2021/8883962 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832563179913216000 |
|---|---|
| author | Ke Xie Yu-sen Chai Shi-hui Lin Fang Xu Chuan-jiang Wang |
| author_facet | Ke Xie Yu-sen Chai Shi-hui Lin Fang Xu Chuan-jiang Wang |
| author_sort | Ke Xie |
| collection | DOAJ |
| description | Objectives. Inflammatory disease characterized by clinical destructive respiratory disorder is called acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Studies have shown that luteolin exerts anti-inflammatory effects by increasing regulatory T cells (Tregs). In this study, we aimed to determine the effects of luteolin on ALI/ARDS and Treg differentiation. Methods. In this paper, we used cecal ligation puncture (CLP) to generate an ALI mouse model to determine the effects of luteolin on ALI/ARDS. Lung tissues were stained for interleukin- (IL-) 17A and myeloperoxidase (MPO) by immunohistochemical analysis. The levels of Treg-related cytokines in serum and bronchoalveolar lavage fluid (BALF) of mice were detected. The protein levels of NF-κB p65 in lung tissues were measured. Macrophage phenotypes in lung tissues were measured using immunofluorescence. The proportion of Tregs in splenic mononuclear cells and peripheral blood mononuclear cells (PBMCs) was quantified. Furthermore, in vitro, we evaluated the effects of luteolin on Treg differentiation, and the effects of IL-10 immune regulation on macrophage polarization were examined. Results. Luteolin alleviated lung injury and suppressed uncontrolled inflammation and downregulated IL-17A, MPO, and NF-κB in the lungs of CLP-induced mouse models. At this time, luteolin upregulated the level of IL-10 in serum and BALF and the frequency of CD4+CD25+FOXP3+ Tregs in PBMCs and splenic mononuclear cells of CLP mice. Luteolin treatment decreased the proportion of M1 macrophages and increased the proportion of M2 macrophages in lungs of CLP-induced mouse models. In vitro, administration of luteolin significantly induced Treg differentiation, and IL-10 promoted the polarization of M2 macrophages but reduced the polarization of M1 macrophages. Conclusions. Luteolin alleviated lung injury and suppressed uncontrolled inflammation by inducing the differentiation of CD4+CD25+FOXP3+ Tregs and upregulating the expression of IL-10. Furthermore, the anti-inflammatory cytokine IL-10 promoted polarization of M2 macrophages in vitro. Luteolin-induced Treg differentiation from naïve CD4+ T cells may be a potential mechanism for regulating IL-10 production. |
| format | Article |
| id | doaj-art-cb1c90c39c574cadb8b1547f86f5fee1 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-cb1c90c39c574cadb8b1547f86f5fee12025-02-03T01:20:48ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/88839628883962Luteolin Regulates the Differentiation of Regulatory T Cells and Activates IL-10-Dependent Macrophage Polarization against Acute Lung InjuryKe Xie0Yu-sen Chai1Shi-hui Lin2Fang Xu3Chuan-jiang Wang4Department of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaObjectives. Inflammatory disease characterized by clinical destructive respiratory disorder is called acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Studies have shown that luteolin exerts anti-inflammatory effects by increasing regulatory T cells (Tregs). In this study, we aimed to determine the effects of luteolin on ALI/ARDS and Treg differentiation. Methods. In this paper, we used cecal ligation puncture (CLP) to generate an ALI mouse model to determine the effects of luteolin on ALI/ARDS. Lung tissues were stained for interleukin- (IL-) 17A and myeloperoxidase (MPO) by immunohistochemical analysis. The levels of Treg-related cytokines in serum and bronchoalveolar lavage fluid (BALF) of mice were detected. The protein levels of NF-κB p65 in lung tissues were measured. Macrophage phenotypes in lung tissues were measured using immunofluorescence. The proportion of Tregs in splenic mononuclear cells and peripheral blood mononuclear cells (PBMCs) was quantified. Furthermore, in vitro, we evaluated the effects of luteolin on Treg differentiation, and the effects of IL-10 immune regulation on macrophage polarization were examined. Results. Luteolin alleviated lung injury and suppressed uncontrolled inflammation and downregulated IL-17A, MPO, and NF-κB in the lungs of CLP-induced mouse models. At this time, luteolin upregulated the level of IL-10 in serum and BALF and the frequency of CD4+CD25+FOXP3+ Tregs in PBMCs and splenic mononuclear cells of CLP mice. Luteolin treatment decreased the proportion of M1 macrophages and increased the proportion of M2 macrophages in lungs of CLP-induced mouse models. In vitro, administration of luteolin significantly induced Treg differentiation, and IL-10 promoted the polarization of M2 macrophages but reduced the polarization of M1 macrophages. Conclusions. Luteolin alleviated lung injury and suppressed uncontrolled inflammation by inducing the differentiation of CD4+CD25+FOXP3+ Tregs and upregulating the expression of IL-10. Furthermore, the anti-inflammatory cytokine IL-10 promoted polarization of M2 macrophages in vitro. Luteolin-induced Treg differentiation from naïve CD4+ T cells may be a potential mechanism for regulating IL-10 production.http://dx.doi.org/10.1155/2021/8883962 |
| spellingShingle | Ke Xie Yu-sen Chai Shi-hui Lin Fang Xu Chuan-jiang Wang Luteolin Regulates the Differentiation of Regulatory T Cells and Activates IL-10-Dependent Macrophage Polarization against Acute Lung Injury Journal of Immunology Research |
| title | Luteolin Regulates the Differentiation of Regulatory T Cells and Activates IL-10-Dependent Macrophage Polarization against Acute Lung Injury |
| title_full | Luteolin Regulates the Differentiation of Regulatory T Cells and Activates IL-10-Dependent Macrophage Polarization against Acute Lung Injury |
| title_fullStr | Luteolin Regulates the Differentiation of Regulatory T Cells and Activates IL-10-Dependent Macrophage Polarization against Acute Lung Injury |
| title_full_unstemmed | Luteolin Regulates the Differentiation of Regulatory T Cells and Activates IL-10-Dependent Macrophage Polarization against Acute Lung Injury |
| title_short | Luteolin Regulates the Differentiation of Regulatory T Cells and Activates IL-10-Dependent Macrophage Polarization against Acute Lung Injury |
| title_sort | luteolin regulates the differentiation of regulatory t cells and activates il 10 dependent macrophage polarization against acute lung injury |
| url | http://dx.doi.org/10.1155/2021/8883962 |
| work_keys_str_mv | AT kexie luteolinregulatesthedifferentiationofregulatorytcellsandactivatesil10dependentmacrophagepolarizationagainstacutelunginjury AT yusenchai luteolinregulatesthedifferentiationofregulatorytcellsandactivatesil10dependentmacrophagepolarizationagainstacutelunginjury AT shihuilin luteolinregulatesthedifferentiationofregulatorytcellsandactivatesil10dependentmacrophagepolarizationagainstacutelunginjury AT fangxu luteolinregulatesthedifferentiationofregulatorytcellsandactivatesil10dependentmacrophagepolarizationagainstacutelunginjury AT chuanjiangwang luteolinregulatesthedifferentiationofregulatorytcellsandactivatesil10dependentmacrophagepolarizationagainstacutelunginjury |