ArticlePLoS pathogens2013
HIF-1α is essential for effective PMN bacterial killing, antimicrobial peptide production and apoptosis in Pseudomonas aeruginosa keratitis.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 74 citations in OpenAlex.
- Roles of endothelial cells during infection.Current opinion in immunology · 2025Review
- Exploring the Ascorbate Requirement of the 2-Oxoglutarate-Dependent Dioxygenases.Journal of medicinal chemistry · 2025Review
- Hypoxia-inducible factor-driven glycolytic adaptations in host-microbe interactions.Pflugers Archiv : European journal of physiology · 2024Review
- The Role ofPharmaceutics · 2024Review
- FOXK2 targeting by the SCF-E3 ligase subunit FBXO24 for ubiquitin mediated degradation modulates mitochondrial respiration.The Journal of biological chemistry · 2024Article
- Quercetin attenuates Pseudomonas aeruginosa-induced acute lung inflammation by inhibiting PI3K/AKT/NF-κB signaling pathway.Inflammopharmacology · 2024Article
- Unraveling the role of HIF-1α in sepsis: from pathophysiology to potential therapeutics-a narrative review.Critical care (London, England) · 2024Review
- The Host-Pathogen Interplay: A Tale of Two Stories within the Cornea and Posterior Segment.Microorganisms · 2023Review
- Glycyrrhizin Interacts with TLR4 and TLR9 to ResolvePathogens (Basel, Switzerland) · 2022Article
- Article
- Hypoxia adaptation in the cornea: Current animal models and underlying mechanisms.Animal models and experimental medicine · 2021Review
- Adjunctive Thymosin Beta-4 Treatment Influences MΦ Effector Cell Function to Improve Disease Outcome inInternational journal of molecular sciences · 2021Article
- Mechanisms controlling bacterial infection in myeloid cells under hypoxic conditions.Cellular and molecular life sciences : CMLS · 2021Review
- Anti-International journal of molecular sciences · 2021Article
- Hypoxia-Inducible Factor 1 Alpha Is Dispensable for Host Defense of Group B Streptococcus Colonization and Infection.Journal of innate immunity · 2021Article
- The Antimicrobial Peptide Human β-Defensin-3 Accelerates Wound Healing by Promoting Angiogenesis, Cell Migration, and Proliferation Through the FGFR/JAK2/STAT3 Signaling Pathway.Frontiers in immunology · 2021Article
- Hypoxia-Inducible Factor-1Mediators of inflammation · 2021Article
- Antimicrobial Resistance in ESKAPE Pathogens.Clinical microbiology reviews · 2020Review
- The Impact of Hypoxia on Neutrophil Degranulation and Consequences for the Host.International journal of molecular sciences · 2020Review
- Hypoxia-inducible factor 1 alpha limits dendritic cell stimulation of CD8 T cell immunity.PloS one · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Hypoxia-inducible factor (HIF)-1α, is a transcription factor that controls energy metabolism and angiogenesis under hypoxic conditions, and a potent regulator of innate immunity. The studies described herein examined the role of HIF-1α in disease resolution in BALB/c (resistant, cornea heals) mice after ocular infection with Pseudomonas (P.) aeruginosa. Furthermore, the current studies focused on the neutrophil (PMN), the predominant cell infiltrate in keratitis. Using both siRNA and an antagonist (17-DMAG), the role of HIF-1α was assessed in P. aeruginosa-infected BALB/c mice. Clinical score and slit lamp photography indicated HIF-1α inhibition exacerbated disease and corneal destruction. Real time RT-PCR, immunohistochemistry, ELISA, Greiss and MPO assays, bacterial load, intracellular killing, phagocytosis and apoptosis assays further tested the regulatory role of HIF-1α. Despite increased pro-inflammatory cytokine expression and increased MPO levels after knocking down HIF-1α expression, in vivo studies revealed a decrease in NO production and higher bacterial load. In vitro studies using PMN provided evidence that although inhibition of HIF-1α did not affect phagocytosis, both bacterial killing and apoptosis were significantly affected, as was production of antimicrobial peptides. Overall, data provide evidence that inhibition of HIF-1α converts a normally resistant disease response to susceptible (corneal thinning and perforation) after induction of bacterial keratitis. Although this inhibition does not appear to affect PMN transmigration or phagocytosis, both in vivo and in vitro approaches indicate that the transcriptional factor is essential for effective bacterial killing, apoptosis and antimicrobial peptide production.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.