Monocytes Undergo Functional Reprogramming to Generate Immunosuppression through HIF-1<i>α</i> Signaling Pathway in the Late Phase of Sepsis

Li, Lili; Dai, Bing; Sun, Yan; Zhang, Tingting

doi:10.1155/2020/4235909

Cited by 9 publications

(6 citation statements)

References 27 publications

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“…Hypoxia facilitates malignant tumor escape from immune surveillance 15–17 . Hypoxia decreases natural killer (NK) and T cell survival and weakens the immune function of dendritic cells (DCs) through a mechanism involving hypoxia‐inducible factor‐1 (HIF‐1) 18 .…”

Section: Introductionmentioning

confidence: 99%

The role of hypoxia‐inducible factor 1 in tumor immune evasion

Wang

et al. 2020

Medicinal Research Reviews

184

136

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Hypoxia‐inducible factor 1 (HIF‐1) plays an indispensable role in the hypoxic tumor microenvironment. Hypoxia and HIF‐1 are involved in multiple aspects of tumor progression, such as metastasis, angiogenesis, and immune evasion. In innate and adaptive immune systems, malignant tumor cells avoid their recognition and destruction by HIF‐1. Tumor immune evasion allows cancer cells to proliferate and metastasize and is associated with immunotherapy failure and chemoresistance. In the hypoxic tumor microenvironment, HIF‐1 signaling suppresses the innate and adaptive immune systems to evade immune attack by inducing the expression of immunosuppressive factors and immune checkpoint molecules, including vascular endothelial growth factor, prostaglandin E2, and programmed death‐ligand 1/programmed death‐1. Moreover, HIF‐1 blocks tumor‐associated antigen presentation via major histocompatibility complex class I chain‐related/natural killer group 2, member D signaling. Tumor‐associated autophagy and the release of tumor‐derived exosomes contribute to HIF‐1‐mediated immune evasion. This review focuses on recent findings on the potential mechanism(s) underlying the effect of hypoxia and HIF‐1 signaling on tumor immune evasion in the hypoxic tumor microenvironment. The effects of HIF‐1 on immune checkpoint molecules, immunosuppressive molecules, autophagy, and exosomes have been described. Additionally, the potential role of HIF‐1 in the regulation of tumor‐derived exosomes, as well as the roles of HIF‐1 and exosomes in tumor evasion, are discussed. This study will contribute to our understanding of HIF‐1‐mediated tumor immune evasion, leading to the development of effective HIF‐1‐targeting drugs and immunotherapies.

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Section: Introductionmentioning

confidence: 99%

The role of hypoxia‐inducible factor 1 in tumor immune evasion

Wang

et al. 2020

Medicinal Research Reviews

184

136

View full text Add to dashboard Cite

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“…It is lately documented that HDAC4 elevation causes H9C2 cell death and mitochondrial dysfunction in hypoxia/reoxygenation injury [ 15 ]. Hypoxia-inducing factor 1 (HIF-1) signaling pathway is the channel that monocytes undergo reprogramming to generate immunosuppression in the late stage of sepsis [ 16 ]. It has been proved that downregulating the activated HIF-1α, the HDAC4 client transcription factor, could improve the prognosis of sepsis [ 17 ] and relieve myocardial injury during sepsis [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

microRNA-124-3p attenuates myocardial injury in sepsis via modulating SP1/HDAC4/HIF-1α axis

Huang

Wen-fang

et al. 2022

Cell Death Discov.

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Sepsis-induced cardiac dysfunction can lead to death in sepsis. In this case, we targeted to explore in detail the relative mechanism of microRNA (miR)-124-3p in sepsis-induced myocardial injury via the specific protein 1/histone deacetylase 4/hypoxia-inducing factor 1α (SP1/HDAC4/HIF-1α) axis. Septic rats were modeled by cecal ligation puncture while in vitro septic cardiomyocyte H9C2 were induced by lipopolysaccharide (LPS). miR-124-3p/SP1/HDAC4/HIF-1α expression levels in myocardial tissues of septic rats and LPS-treated H9C2 cells were measured. miR-124-3p overexpression and SP1 silencing assays were implemented on LPS-treated H9C2 cells to explore theirs actions in inflammation, oxidative stress and cell apoptosis. The interactions of miR-124-3p, SP1, and HDAC4 were testified. miR-124-3p was lowly expressed while SP1, HDAC4, and HIF-1α were highly expressed in sepsis. Upregulation of miR-124-3p ameliorated inflammation, oxidative stress, and apoptosis of LPS-treated H9C2 cells. Silencing SP1 improved LPS-induced damage to cardiomyocytes. miR-124-3p targeted SP1 and HDAC4 interacted with SP1. SP1 overexpression antagonized miR-124-3p upregulation-induced improvements in LPS-induced cardiomyocyte damage. This study illustrates that miR-124-3p improves myocardial injury in septic rats through targeted regulation of SP1 to mediate HDAC4/HIF-1α.

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“…Interestingly, our bioinformatics analyses (Fig. S5 ) and literature [ 28 ] showed that both miR-150-5p and miR-21-5p modulated HIF-1 cellular signaling pathway, whilst the HIF-1α signaling pathway was shown to be attributable to the immunosuppression through the immune cell (e.g., monocytes) phenotype changes reprogramming in the late stage of sepsis.…”

Section: Discussionmentioning

confidence: 73%

miR-150-5p in neutrophil-derived extracellular vesicles associated with sepsis-induced cardiomyopathy in septic patients

Lin

Xiao

et al. 2023

Cell Death Discov.

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Introduction Early diagnosis and potential therapeutic targets of sepsis-induced cardiomyopathy (SIC) remain challenges clinically. Circulating extracellular vesicles from immune cells carrying crucial injurious mediators, including miRNAs in sepsis. However, the impacts of neutrophil-derived extracellular vesicles and their miRNAs in the SIC development are unknown. Objectives The present study focused on the in-depth miRNA expression profiles of neutrophil-derived extracellular vesicles and explored the potential molecular biomarkers during the process of SIC. Methods Neutrophil-derived extracellular vesicles were isolated from the blood samples in three sepsis patients with or without cardiomyopathy on day 1 and day 3 after ICU admission in comparison with three healthy controls. miRNAs were determined by RNA sequencing. The closely related differentially expressed miRNAs with SIC were further validated through qRT-PCR in the other cohorts of sepsis patients with (30 patients) or without cardiomyopathy (20 patients) and the association between miRNAs and the occurrence or disease severity of septic cardiomyopathy were stratified with logistic regression analysis. Results Sixty-eight miRNAs from neutrophil-derived extracellular vesicles were changed significantly between healthy controls and without septic cardiomyopathy patients (61 miRNAs upregulated and seven downregulated). Thirty-eight miRNAs were differentially expressed in the septic cardiomyopathy patients. 27 common differentially expressed miRNAs were found in both groups with similar kinetics (23 miRNAs upregulated and four downregulated). The enriched cellular signaling pathway mediated by miRNAs from sepsis to septic cardiomyopathy was the HIF-1 signaling system modulated septic inflammation. Using multivariate logistic regression analysis, miR-150-5p coupled with NT-pro BNP, LVEF, and SOFA score (AUC = 0.941) were found to be the independent predictors of septic cardiomyopathy. Conclusion miRNAs derived from neutrophil-derived extracellular vesicles play an important role in septic disease severity development towards cardiomyopathy. miR-150-5p may be a predictor of sepsis severity development but warrants further study.

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Monocytes Undergo Functional Reprogramming to Generate Immunosuppression through HIF-1α Signaling Pathway in the Late Phase of Sepsis

Cited by 9 publications

References 27 publications

The role of hypoxia‐inducible factor 1 in tumor immune evasion

The role of hypoxia‐inducible factor 1 in tumor immune evasion

microRNA-124-3p attenuates myocardial injury in sepsis via modulating SP1/HDAC4/HIF-1α axis

miR-150-5p in neutrophil-derived extracellular vesicles associated with sepsis-induced cardiomyopathy in septic patients

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