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Cited by 379Cancer, Hypoxia, and MetabolismImmune cells in cancerInflammation biomarkers and pathways

Hypoxia-Inducible Factors as Essential Regulators of Inflammation

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Imtiyaz, Hongxia Z., Simon, M. Celeste·2010·Current Topics in Microbiology and Immunology
DOI 10.1007/82_2010_74PMC PMC3144567
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Abstract

Myeloid cells provide important functions in low oxygen (O(2)) environments created by pathophysiological conditions, including sites of infection, inflammation, tissue injury, and solid tumors. Hypoxia-inducible factors (HIFs) are principle regulators of hypoxic adaptation, regulating gene expression involved in glycolysis, erythropoiesis, angiogenesis, proliferation, and stem cell function under low O(2). Interestingly, increasing evidence accumulated over recent years suggests an additional important regulatory role for HIFs in inflammation. In macrophages, HIFs not only regulate glycolytic energy generation, but also optimize innate immunity, control pro-inflammatory gene expression, mediate bacterial killing and influence cell migration. In neutrophils, HIF-1α promotes survival under O(2)-deprived conditions and mediates blood vessel extravasation by modulating β (2) integrin expression. Additionally, HIFs contribute to inflammatory functions in various other components of innate immunity, such as dendritic cells, mast cells, and epithelial cells. This review will dissect the role of each HIF isoform in myeloid cell function and discuss their impact on acute and chronic inflammatory disorders. Currently, intensive studies are being conducted to illustrate the connection between inflammation and tumorigenesis. Detailed investigation revealing interaction between microenvironmental factors such as hypoxia and immune cells is needed. We will also discuss how hypoxia and HIFs control properties of tumor-associated macrophages and their relationship to tumor formation and progression.

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  • HIF-2α preferentially persists during chronic inflammation, tumor growth, and sustained oxidative signaling, where redox tone outweighs oxygen tension.

    “These findings anticipated later observations that HIF-2α preferentially persists during chronic inflammation, tumor growth, and sustained oxidative signaling, where redox tone outweighs oxygen tension [206].”

    From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [206]

    The ‘HIF-2 α activity in TAMs’ section reports strong HIF-2α expression in tumor-associated macrophages across human tumors, supporting the tumor context. It does not establish preferential persistence during chronic inflammation or sustained oxidative signaling. The ‘Inflammatory stimuli-induced HIF activity’ section discusses ROS-mediated induction of HIF-1α, not HIF-2α, and the paper does not say redox tone outweighs oxygen tension. (LLM, conf=0.86)

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Authors
Imtiyaz, H. Z., & Simon, M. C.
Affiliations
  • University of Pennsylvania (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Simon, M. Celeste
ORCID
Simon, M. Celeste
Venue
Current Topics in Microbiology and Immunology
Publisher
Springer Berlin Heidelberg
Published
2010
Volume
345
Pages
105-120
ISSN
0070-217X (ISSN-L)
DOI
10.1007/82_2010_74
PMC
PMC3144567
OpenAlex
W44391579
Cited by
379
References
90
Citations by year
2026: 10 · 2025: 11 · 2024: 23 · 2023: 24 · 2022: 33 · 2021: 40 · 2020: 37 · 2019: 24 · 2018: 24 · 2017: 27 · 2016: 31 · 2015: 15 · 2014: 25 · 2013: 24 · 2012: 17
FWCI
24.00
Type
book chapter
Language
en
Open access
Locations
  • Current topics in microbiology and immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
Howard Hughes Medical Institute
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Keywords
hypoxia-inducible factor, HIF-1α, HIF-2α, hypoxia, inflammation, myeloid cells, macrophages, neutrophils, innate immunity, glycolysis, beta2 integrins, extravasation, dendritic cells, mast cells, epithelial cells, tumor-associated macrophages, inflammation and tumorigenesis, chronic inflammation
MeSH terms
Endothelial PAS Domain-Containing Protein 1, Animals, Humans, Inflammation, Macrophages, Neoplasms, Cell Hypoxia, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1, alpha Subunit

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