Luteolin activates Tregs to promote IL-10 expression and alleviating caspase-11-dependent pyroptosis in sepsis-induced lung injury

Zhang, Zhengtao; Zhang, Danying; Xie, Kexin; Wang, Chuanjiang; Xu, Fang

doi:10.1016/j.intimp.2021.107914

Cited by 58 publications

(35 citation statements)

References 48 publications

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“…Cecal ligation and puncture (CLP) is the commonly used method to induce polymicrobial sepsis containing gram-negative bacteria-related sepsis. The cecum ligated area and puncture number are responsible for the intensity of sepsis (Zhang et al, 2021a). The peripheral injection of bacterial endotoxin lipopolysaccharide (LPS) is also frequently applied to mimic sepsis in the murine model.…”

Section: Introductionmentioning

confidence: 99%

“…The neutrophils and macrophages are major cells located in the alveoli and are frequently found in the bronchoalveolar lavage fluid (BALF). The activation of neutrophil and macrophage is the pathological hallmark of the immune/inflammatory response in ALI (Fowler et al, 2019;Zhang et al, 2021a). Despite huge efforts being made, the etiology of sepsis-induced ALI is still not fully understood.…”

Section: Introductionmentioning

confidence: 99%

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The Effect of Shionone on Sepsis-Induced Acute Lung Injury by the ECM1/STAT5/NF-κB Pathway

Song

Jiang

et al. 2022

Front. Pharmacol.

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Purpose: The purpose of the present study was to estimate the effect of shionone (SHI) on sepsis-induced acute lung injury (ALI).Methods: The cecal ligation and puncture (CLP) surgery was performed to induce sepsis in mice. Pulmonary hematoxylin and eosin staining, the wet/dry ratio, myeloperoxidase (MPO) activity, and the survival rate were detected. The RAW264.7 cells were treated with SHI and stimulated with lipopolysaccharide (LPS). The cells were also overexpressed by extracellular mechanism protein 1 (ECM1) adenovirus. The relative levels of granulocyte–macrophage colony-stimulating factor, IL-6, IL-1β, TNF-α, IL-10, and TGF-β in the serum and supernatant were measured by ELISA. The protein expressions of ECM1, p-STAT5, signal transducer and activator of transcription 5 (STAT5), p-NF-κB, nuclear factor kappa-B (NF-κB), Arg1, CD206, CD16/32, and iNOS in the CLP-induced lung tissues and LPS-induced cells were detected by western blot. The cell counts of Ly6G, F4/80, CD16/32, and CD206 were evaluated by flow cytometry. The ECM1 expression was also observed by immunohistochemistry and immunofluorescence staining.Results: As a result, the histopathological change, pulmonary edema, and the MPO activity were relieved by SHI. SHI treatment increased the percentage of neutrophil and macrophage in the bronchoalveolar lavage fluid. Besides, SHI administration inhibited pro-inflammatory cytokines and M1 phenotype indices, as well as augmented the anti-inflammatory cytokines and M2 phenotype indices. SHI also attenuated the ECM1/STAT5/NF-κB pathway both in vivo and in vitro. The overexpression of ECM1 confirmed that the regulated effect of SHI was due to ECM1 signaling.Conclusion: In conclusion, the present study suggests that SHI ameliorated sepsis-induced ALI by screwing M1 phenotype to M2 phenotype macrophage via the ECM1/STAT5/NF-κB pathway.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Effect of Shionone on Sepsis-Induced Acute Lung Injury by the ECM1/STAT5/NF-κB Pathway

Song

Jiang

et al. 2022

Front. Pharmacol.

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“…Hotchkiss et al reported that Tregs impair immunity and contribute to contribute to nosocomial infections and mortality [33]. However, several studies have shown that activated Tregs prevent polymicrobial sepsis mortality [32,34], and regulate the activation status and antigen-presenting cell function and produce anti-inflammatory cytokines, which are beneficial to sepsis [35][36][37]. FOXP3 and CTLA-4 were used as biomarkers for defining Tregs function [38].…”

Section: Discussionmentioning

confidence: 99%

Gentamicin promoted the production of CD4+CD25+ Tregs via the STAT5 signaling pathway in mice sepsis

Liu

et al. 2022

BMC Immunol

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Background Increasing studies have reported that gentamicin (GNT) plays an essential role in sepsis; however, its underlying mechanism is still unclear. In this study, we investigated the mechanism of GNT in sepsis. Results We observed that GNT enhanced survival and alleviated inflammatory injuries of the lungs, liver, kidneys, and intestines in mice with sepsis. Furthermore, regulatory T cells (Tregs) showed enhanced inhibitory function, and pro-inflammatory cytokines IL-1β, TNF-α, and IL-2 and anti-inflammatory cytokine IL-10 showed decreased and increased peritoneal fluid levels, respectively, after treatment with GNT. GNT showed enhanced phosphorylation of signal transducer and activator of transcription 5 (p-STAT5) in Tregs in vivo and in vitro. The STAT5 inhibitor restrained the increased functional changes of Tregs and reduced inflammatory responses induced by GNT in vitro. Moreover, the STAT5 inhibitor reversed GNT-mediated impacts on survival and inflammation, and the percentage, apoptosis, and phenotypic and functional changes of Tregs in neonatal sepsis. Conclusions Our study revealed that GNT regulates the function of Tregs via the STAT5 signaling pathway, alleviating inflammatory injuries, and provides novel evidence in the treatment of neonatal sepsis.

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“…However, non-canonical inflammasomes have not received much attention in studies investigating the inhibitory role of ginseng in inflammasome activation and inflammasome-activated inflammatory diseases. Several natural compounds, such as flavonoids and plant extracts, have been reported to attenuate inflammatory responses and diseases by inhibiting non-canonical inflammasome [ [82] , [83] , [84] , [85] , [86] , [87] , [88] ]; however, the inhibitory role of ginseng in non-canonical inflammasome activation has been rarely demonstrated. KRG extract hindered caspase-11 non-canonical inflammasome initiation and downstream inflammatory responses in macrophages (article in press; https://doi.org/10.1016/j.jgr.2021.12.009 ).…”

Section: Inhibitory Role Of Ginseng In Inflammasome Activationmentioning

confidence: 99%

Potential benefits of ginseng against COVID-19 by targeting inflammasomes

2022

Journal of Ginseng Research

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Luteolin activates Tregs to promote IL-10 expression and alleviating caspase-11-dependent pyroptosis in sepsis-induced lung injury

Cited by 58 publications

References 48 publications

The Effect of Shionone on Sepsis-Induced Acute Lung Injury by the ECM1/STAT5/NF-κB Pathway

The Effect of Shionone on Sepsis-Induced Acute Lung Injury by the ECM1/STAT5/NF-κB Pathway

Gentamicin promoted the production of CD4+CD25+ Tregs via the STAT5 signaling pathway in mice sepsis

Potential benefits of ginseng against COVID-19 by targeting inflammasomes

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