The role of HIF in immunity and inflammation

Cummins, Eoin P.; Keogh, Ciara E.; Crean, Daniel; Taylor, Cormac T.

doi:10.1016/j.mam.2015.12.004

Cited by 130 publications

(98 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…HIF has cell type-specific roles, which have a profound impact on immune cell gene expression and downstream effector function. The specific functions of HIF in individual immune cell types has been recently reviewed and will be discussed only briefly here (reviewed in REFS 11,12). In neutrophils, HIF has a key role in the regulation of lifespan, antimicrobial peptide production and apoptosis 47,48 .…”

Section: Hif Modulation Of Immune Cell Functionmentioning

confidence: 99%

Regulation of immunity and inflammation by hypoxia in immunological niches

2017

Self Cite

View full text Add to dashboard Cite

Immunological niches are focal sites of immune activity that can have varying microenvironmental features. Hypoxia is a feature of physiological and pathological immunological niches. The impact of hypoxia on immunity and inflammation can vary depending on the microenvironment and immune processes occurring in a given niche. In physiological immunological niches, such as the bone marrow, lymphoid tissue, placenta and intestinal mucosa, physiological hypoxia controls innate and adaptive immunity by modulating immune cell proliferation, development and effector function, largely via transcriptional changes driven by hypoxia-inducible factor (HIF). By contrast, in pathological immunological niches, such as tumours and chronically inflamed, infected or ischaemic tissues, pathological hypoxia can drive tissue dysfunction and disease development through immune cell dysregulation. Here, we differentiate between the effects of physiological and pathological hypoxia on immune cells and the consequences for immunity and inflammation in different immunological niches. Furthermore, we discuss the possibility of targeting hypoxia-sensitive pathways in immune cells for the treatment of inflammatory disease.

show abstract

Section: Hif Modulation Of Immune Cell Functionmentioning

confidence: 99%

Regulation of immunity and inflammation by hypoxia in immunological niches

2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Both inflammation and cancer are metabolically costly processes, which require increased oxygen consumption. In conjunction with some vascular dysfunction, it predisposes tissue to hypoxia and further activation of hypoxia-inducible transcription factors (HIF)s. Cross-talk between NF-κB and HIFs attracts more attention nowadays [93,94]. …”

Section: Pro-inflammatory Mediators and Growth Factors In The Gastmentioning

confidence: 99%

NF‐κB Signaling in Gastric Cancer

Sokolova

Naumann

2017

Toxins

182

122

View full text Add to dashboard Cite

Gastric cancer is a leading cause of cancer death worldwide. Diet, obesity, smoking and chronic infections, especially with Helicobacter pylori, contribute to stomach cancer development. H. pylori possesses a variety of virulence factors including encoded factors from the cytotoxin-associated gene pathogenicity island (cagPAI) or vacuolating cytotoxin A (VacA). Most of the cagPAI-encoded products form a type 4 secretion system (T4SS), a pilus-like macromolecular transporter, which translocates CagA into the cytoplasm of the host cell. Only H. pylori strains carrying the cagPAI induce the transcription factor NF-κB, but CagA and VacA are dispensable for direct NF-κB activation. NF-κB-driven gene products include cytokines/chemokines, growth factors, anti-apoptotic factors, angiogenesis regulators and metalloproteinases. Many of the genes transcribed by NF-κB promote gastric carcinogenesis. Since it has been shown that chemotherapy-caused cellular stress could elicit activation of the survival factor NF-κB, which leads to acquisition of chemoresistance, the NF-κB system is recommended for therapeutic targeting. Research is motivated for further search of predisposing conditions, diagnostic markers and efficient drugs to improve significantly the overall survival of patients. In this review, we provide an overview about mechanisms and consequences of NF-κB activation in gastric mucosa in order to understand the role of NF-κB in gastric carcinogenesis.

show abstract

“…A dominant and consistent theme that has evolved is that HIFs play a central role in the regulation of immune cell development and function; consequently, HIFs should be considered key regulators of immunity and inflammation. These studies revealed cell type-specific roles for HIF in the regulation of a number of processes central to immune cell activity (27). While our understanding of the role of HIFs in immune cell function is expanding, it is notable that during inflammation, hypoxia occurs not in isolation but in the complex milieu of the inflammatory lesion.…”

Section: Hif and Barrier Functionmentioning

confidence: 99%

“…Because of the role of hydroxylases in the regulation of hypoxia-responsive transcription factors, these enzymes also play a key role in the regulation of immune cell activity (27). While our understanding of the role of HIF hydroxylases in the regulation of immune cell function is far from complete, recent studies investigating individual HIF hydroxylase isoforms in discreet immune and epithelial cell subtypes have identified isoform-specific roles (80)(81)(82)(83)(84)(85)(86)(87)(88)(89).…”

Section: Regulation Of Immune Cell Function By Phdsmentioning

confidence: 99%