Hypoxia-Inducible Factor-1 Alpha Stabilization in Human Macrophages during Leishmania major Infection Is Impaired by Parasite Virulence.

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  • Additional Information
    • Source:
      Publisher: Korean Society for Parasitology Country of Publication: Korea (South) NLM ID: 9435800 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1738-0006 (Electronic) Linking ISSN: 00234001 NLM ISO Abbreviation: Korean J Parasitol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Seoul, Korea : Korean Society for Parasitology, c1993-2022.
    • Subject Terms:
      Leishmania major* ; Parasites* ; Leishmaniasis*; Animals ; Humans ; Vascular Endothelial Growth Factor A ; Virulence ; Macrophages ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Hypoxia/metabolism
    • Abstract:
      Hypoxia-inducible factor-1 alpha (HIF-1α) is one of the master regulators of immune and metabolic cellular functions. HIF-1α, a transcriptional factor whose activity is closely related to oxygen levels, is a target for understanding infectious disease control. Several studies have demonstrated that HIF-1α plays an important role during the infectious process, while its role in relation to parasite virulence has not been addressed. In this work, we studied the expression levels of HIF-1α and related angiogenic vascular endothelial growth factor A (VEGF-A) in human macrophages infected with promastigotes of hypo- or hyper-virulent Leishmania major human isolates. L. major parasites readily subverted host macrophage functions for their survival and induced local oxygen consumption at the site of infection. In contrast to hypo-virulent parasites that induce high HIF-1α expression levels, hyper-virulent L. major reduced HIF-1α expression in macrophages under normoxic or hypoxic conditions, and consequently impeded the expression of VEGF-A mRNA. HIF-1α may play a key role during control of disease chronicity, severity, or outcome.
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    • Grant Information:
      Tunisian Ministry of Higher Education and Research
    • Contributed Indexing:
      Keywords: HIF-1α; Leishmania major; VEGF-A; hypoxia; macrophage; virulence
    • Accession Number:
      0 (Vascular Endothelial Growth Factor A)
      0 (Hypoxia-Inducible Factor 1, alpha Subunit)
    • Publication Date:
      Date Created: 20221102 Date Completed: 20221103 Latest Revision: 20221109
    • Publication Date:
      20231215
    • Accession Number:
      PMC9633161
    • Accession Number:
      10.3347/kjp.2022.60.5.317
    • Accession Number:
      36320108