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Cited by 18HIV Research and TreatmentMicroRNA in disease regulationGenomics, phytochemicals, and oxidative stress

HIV Impairs Alveolar Macrophage Function via MicroRNA-144-Induced Suppression of Nrf2

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Fan, Xian, Murray, Shannon C., Staitieh, Bashar S., Spearman, Paul, Guidot, David M.·2021·The American Journal of the Medical Sciences
DOI 10.1016/j.amjms.2020.07.026PMC PMC7854972
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Abstract

Background Despite anti-retroviral therapy, HIV-1 infection increases the risk of pneumonia and causes oxidative stress and defective alveolar macrophage (AM) immune function. We have previously determined that HIV-1 proteins inhibit antioxidant defenses and impair AM phagocytosis by suppressing nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Given its known effects on Nrf2, we hypothesize miR-144 mediates the HIV-1 induced suppression of Nrf2. Methods Primary AMs isolated from HIV-1 transgenic (HIV-1 Tg) rats and wild type littermates (WT) as well as human monocyte-derived macrophages (MDMs) infected ex vivo with HIV-1 were used. We modulated miR-144 expression using a miR-144 mimic or an inhibitor to assay its effects on Nrf2/ARE activity and AM functions in vitro and in vivo. Results MiR-144 expression was increased in AMs from HIV-1 Tg rats and in HIV-1-infected human MDMs compared to cells from WT rats and non-infected human MDMs, respectively. Increasing miR-144 with a miR-144 mimic inhibited the expression of Nrf2 and its downstream effectors in WT rat macrophages and consequently impaired their bacterial phagocytic capacity and H 2 O 2 scavenging ability. These effects on Nrf2 expression and AM function were reversed by antagonizing miR-144 ex vivo or in the airways of HIV-1 Tg rats in vivo, but this protection was abrogated by silencing Nrf2 expression. Conclusions Our results suggest that inhibiting miR-144 or interfering with its deleterious effects on Nrf2 attenuates HIV-1-mediated AM immune dysfunction and improves lung health in individuals with HIV.

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  • Increased expression of miR-144 in rat macrophages impairs bacterial phagocytic capacity and H2O2 scavenging ability.

    “increased expression of miR-144 on a rat macrophage model impaired bacterial phagocytic capacity and H2O2 scavenging ability [146].”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [146]

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Cited by

Sorted by citations

Authors
Fan, X., Murray, S. C., Staitieh, B. S., Spearman, P., & Guidot, D. M.
Affiliations
  • Emory University (US)
  • Cincinnati Children's Hospital Medical Center (US)
Corresponding author
Fan, Xian
ORCID
Venue
The American Journal of the Medical Sciences
Publisher
Elsevier BV
Published
2021-01
Volume
361
Issue
1
Pages
90-97
ISSN
0002-9629 (ISSN-L)
DOI
10.1016/j.amjms.2020.07.026
PMC
PMC7854972
OpenAlex
W3044452339
Cited by
18
References
0
Citations by year
2025: 3 · 2024: 6 · 2023: 3 · 2022: 3 · 2021: 3
FWCI
1.19
Type
journal article
Language
en
Open access
Licence
Locations
  • The American Journal of the Medical Sciences (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Alcohol Abuse and Alcoholism
  • National Institute of Allergy and Infectious Diseases
  • National Heart, Lung, and Blood Institute
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Keywords
HIV-1 infection, alveolar macrophages, microRNA-144, Nrf2, oxidative stress, phagocytosis, hydrogen peroxide scavenging, HIV-associated pneumonia, antioxidant defense, HIV-1 transgenic rats, monocyte-derived macrophages, airway immunity
MeSH terms
Animals, Female, HIV, Male, HIV Infections, Macrophages, Alveolar, MicroRNAs, NF-E2-Related Factor 2, Rats

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