Smiglaside A ameliorates LPS-induced acute lung injury by modulating macrophage polarization via AMPK-PPARγ pathway

Background and Aims:Rabdosia japonica var. glaucocalyx is a traditional Chinese medicine (TCM) for various inflammatory diseases. This present work aimed to investigate the protective effects of R. japonica var. glaucocalyx glycoproteins on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the potential mechanism.Methods: Glycoproteins (XPS) were isolated from R. japonica var. glaucocalyx, and homogeneous glycoprotein (XPS5-1) was purified from XPS. ANA-1 cells were used to observe the effect of glycoproteins on the secretion of inflammatory mediators by enzyme-linked immunosorbent assay (ELISA). Flow cytometry assay, immunofluorescence assay, and Western blot analysis were performed to detect macrophage polarization in vitro. The ALI model was induced by LPS via intratracheal instillation, and XPS (20, 40, and 80 mg/kg) was administered intragastrically 2 h later. The mechanisms of XPS against ALI were investigated by Western blot, ELISA, and immunohistochemistry.Results:In vitro, XPS and XPS5-1 downregulated LPS-induced proinflammatory mediators production including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and nitric oxide (NO) and upregulated LPS-induced IL-10 secretion. The LPS-stimulated macrophage polarization was also modulated from M1 to M2. In vivo, XPS maintained pulmonary histology with significantly reducing protein concentration and numbers of mononuclear cells in bronchoalveolar lavage fluid (BALF). The level of IL-10 in BALF was upregulated by XPS treatment. The level of cytokines including TNF-α, IL-1β, and IL-6 was downregulated. XPS also decreased infiltration of macrophages and polymorphonuclear leukocytes (PMNs) in lung. XPS suppressed the expression of key proteins in the TLR4/NF-κB signal pathway.Conclusion: XPS was demonstrated to be a potential agent for treating ALI. Our findings might provide evidence supporting the traditional application of R. japonica var. glaucocalyx in inflammation-linked diseases.

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IL-17 mediated macrophage polarization increased inflammatory damage in SWI-ALI models

10.21203/rs.3.rs-50635/v1 ◽

2020 ◽

Author(s):

Jiayi Zhao ◽

Jin Pu ◽

Rong Zhang ◽

Jian Fan ◽

Yiping Han ◽

...

Keyword(s):

Wound Healing ◽

Acute Lung Injury ◽

Lung Injury ◽

Alveolar Epithelial Cell ◽

Macrophage Polarization ◽

Alveolar Epithelial Cells ◽

In Vitro Test ◽

Alveolar Epithelial ◽

Inflammatory Damage

Abstract BackgroundSeawater inhalation induced acute lung injury (SWI-ALI) is the common accident in daily naval training. To investigate the mechanism of SWI-ALI will help to improve the treatment effect. Alveolar macrophages (AM) is the majority of alveolar, also paly the key role in SWI-ALI repair. IL-17 also paly the key role in the innate immunity process.MethodIn this study, we used seawater induced the ALI in mouse model. And the lungs and serum were exacted at D1, D3, D7 and D14. The AM polarization were tested by flow cytometry. The IL-17 concentration were tested by ELISA. Then the IL-17 function were confirmed by in vitro test. The mouse alveolar epithelial cell and mouse AM were co-cultured. The test compared the wound healing effect of MAE with and without IL-17.ResultThe AM switch into M1 and IL-17A increased were found after seawater dosing. And the IL-17a supplement attenuated wound healing of alveolar epithelial cells through improve the polarization of AM were confirmed in vitro model.ConclusionThe high IL-I7 micro-environment will increased the inflammatory damage through induced macrophage polarization in acute lung injury. The IL-17 antagonists have the potential to increase clinical effect in SWI-ALI treatment.

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Luteolin Regulates the Differentiation of Regulatory T Cells and Activates IL-10-Dependent Macrophage Polarization against Acute Lung Injury

Journal of Immunology Research ◽

10.1155/2021/8883962 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Ke Xie ◽

Yu-sen Chai ◽

Shi-hui Lin ◽

Fang Xu ◽

Chuan-jiang Wang

Keyword(s):

T Cells ◽

Acute Lung Injury ◽

Lung Injury ◽

Mouse Models ◽

Mononuclear Cells ◽

Macrophage Polarization ◽

M2 Macrophages ◽

M1 Macrophages ◽

Treg Differentiation

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.

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