Hypoxia and the hypoxia-regulated transcription factor HIF-1α suppress the host defence of airway epithelial cells

Polke, Markus; Seiler, Frederik; Lepper, Philipp M.; Kamyschnikow, Andreas; Langer, Frank; Monz, Dominik; Herr, Christian; Bals, Robert; Beißwenger, Christoph

doi:10.1177/1753425917698032

Cited by 38 publications

(31 citation statements)

References 49 publications

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“…Airway epithelial cells (AECs) are the initial checkpoints in the defence against pathogens and other inhaled particulates, and these cells are crucial to the regulation of both innate and adaptive immune responses to these challenges [52,53].…”

Section: Airway Epithelial Cellsmentioning

confidence: 99%

Dysregulated signalling pathways in innate immune cells with cystic fibrosis mutations

Lara-Reyna

Holbrook

Jarosz-Griffiths

et al. 2020

Cell. Mol. Life Sci.

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Cystic fibrosis (CF) is one of the most common life-limiting recessive genetic disorders in Caucasians, caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). CF is a multi-organ disease that involves the lungs, pancreas, sweat glands, digestive and reproductive systems and several other tissues. This debilitating condition is associated with recurrent lower respiratory tract bacterial and viral infections, as well as inflammatory complications that may eventually lead to pulmonary failure. Immune cells play a crucial role in protecting the organs against opportunistic infections and also in the regulation of tissue homeostasis. Innate immune cells are generally affected by CFTR mutations in patients with CF, leading to dysregulation of several cellular signalling pathways that are in continuous use by these cells to elicit a proper immune response. There is substantial evidence to show that airway epithelial cells, neutrophils, monocytes and macrophages all contribute to the pathogenesis of CF, underlying the importance of the CFTR in innate immune responses. The goal of this review is to put into context the important role of the CFTR in different innate immune cells and how CFTR dysfunction contributes to the pathogenesis of CF, highlighting several signalling pathways that may be dysregulated in cells with CFTR mutations.

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Section: Airway Epithelial Cellsmentioning

confidence: 99%

Dysregulated signalling pathways in innate immune cells with cystic fibrosis mutations

Lara-Reyna

Holbrook

Jarosz-Griffiths

et al. 2020

Cell. Mol. Life Sci.

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“…Hypoxia promotes the B cell differentiation potential of lymphoid-primed multipotent progenitors through HIF-1α, resulting in the production of B cells (97). Under hypoxic conditions, HIF-1α also regulates innate immune responses, induces regulatory T cells (Tregs), and mediates immune escape from cytotoxic T lymphocytes and other complex immune responses (98)(99)(100). In previous years, HIF-1α-mediated tumor immunity has been proposed as a direction to solve the problems associated with tumor therapy (101)(102)(103), so the immune response of CSCs mediated by HIF-1α is also worth exploring when investigating antitumor therapies.…”

Section: Role Of Hif-1 In Tumor Immunity Of Cscsmentioning

confidence: 99%

Role of hypoxia inducible factor-1 in cancer stem cells (Review)

et al. 2020

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Cancer stem cells (CSCs) have been found to play a decisive role in cancer recurrence, metastasis, and chemo-, radio-and immuno-resistance. Understanding the mechanism of CSC self-renewal and proliferation may help overcome the limitations of clinical treatment. The microenvironment of tumor growth consists of a lack of oxygen, and hypoxia has been confirmed to induce cancer cell invasion, metastasis and epithelial-mesenchymal transition, and is usually associated with poor prognosis and low survival rates. Hypoxia inducible factor-1 (HIF-1) can be stably expressed under hypoxia and act as an important molecule to regulate the development of CSCs, but the specific mechanism remains unclear. The present review attempted to explain the role of HIF-1 in the generation and maintenance of CSCs from the perspective of epigenetics, metabolic reprogramming, tumor immunity, CSC markers, non-coding RNA and signaling pathways associated with HIF-1, in order to provide novel targets with HIF-1 as the core for clinical treatment, and extend the life of patients. Contents 1. Introduction 2. Structural characteristics of HIF-1 3. Role of epigenetic and post-translational modification of HIF-1 in CSCs 4. Role of HIF-1 in non-coding RNA associated with CSCs 5. Role of HIF-1 in CSC markers 6. Role of HIF-1 in tumor immunity of CSCs 7. Role of HIF-1 in metabolic reprogramming of CSCs 8. Role of HIF-1 in signaling pathways associated with CSCs 9. Potential targets for CSC therapy 10. Conclusions and perspectives

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“…In addition to H/R, consecutive hypoxia for a long period has also been reported to modulate the inflammatory functions and oxidant-induced cell injury in airway epithelial cells (Olson et al, 2011;Pahlman et al, 2015;Pandya et al, 2016;Polke et al, 2017). It was shown that consecutive hypoxia for longer than 24 h contributed to the pathogenesis of chronic pulmonary diseases via both the HIF1α-dependent downregulation of the complement regulatory protein CD55 and several inflammatory cytokines, including IL-6, IP-6, IP-10, and hBD-2, as well as the TGFβ1-dependent downregulation of the secretory leukocyte protease inhibitor, in human airway epithelial cells (Pahlman et al, 2015;Pandya et al, 2016;Polke et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Consecutive Hypoxia Decreases Expression of NOTCH3, HEY1, CC10, and FOXJ1 via NKX2-1 Downregulation and Intermittent Hypoxia-Reoxygenation Increases Expression of BMP4, NOTCH1, MKI67, OCT4, and MUC5AC via HIF1A Upregulation in Human Bronchial Epithelial Cells

Yang

Lin

Wang

et al. 2020

Front. Cell Dev. Biol.

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Previous studies have shown that the experimental models of hypoxia-reoxygenation (H/R) mimics the physiological conditions of ischemia-reperfusion and induce oxidative stress and injury in various types of organs, tissues, and cells, both in vivo and in vitro, including human lung adenocarcinoma epithelial cells. Nonetheless, it had not been reported whether H/R affected proliferation, apoptosis, and expression of stem/progenitor cell markers in the bronchial epithelial cells. In this study, we investigated differential effects of consecutive hypoxia and intermittent 24/24-h cycles of H/R on human bronchial epithelial (HBE) cells derived from the same-race and agematched healthy subjects (i.e., NHBE) and subjects with chronic obstructive pulmonary disease (COPD) (i.e., DHBE). To analyze gene/protein expression during differentiation, both the NHBE and DHBE cells at the 2nd passage were cultured at the air-liquid interface (ALI) in the differentiation medium under normoxia for 3 days, followed by either culturing under hypoxia (1% O 2) for consecutively 9 days and then returning to normoxia for another 9 days, or culturing under 24/24-h cycles of H/R (i.e., 24 h of 1% O 2 followed by 24 h of 21% O 2 , repetitively) for 18 days in total, so that all differentiating HBE cells were exposed to hypoxia for a total of 9 days. In both the normal and diseased HBE cells, intermittent H/R significantly increased HIF1A, BMP4, NOTCH1, MKI67, OCT4, and MUC5AC expression, while consecutive hypoxia significantly decreased NKX2-1, NOTCH3, HEY1, CC10, and FOXJ1 expression.

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Hypoxia and the hypoxia-regulated transcription factor HIF-1α suppress the host defence of airway epithelial cells

Cited by 38 publications

References 49 publications

Dysregulated signalling pathways in innate immune cells with cystic fibrosis mutations

Dysregulated signalling pathways in innate immune cells with cystic fibrosis mutations

Role of hypoxia inducible factor-1 in cancer stem cells (Review)

Consecutive Hypoxia Decreases Expression of NOTCH3, HEY1, CC10, and FOXJ1 via NKX2-1 Downregulation and Intermittent Hypoxia-Reoxygenation Increases Expression of BMP4, NOTCH1, MKI67, OCT4, and MUC5AC via HIF1A Upregulation in Human Bronchial Epithelial Cells

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