Activation of Alveolar Macrophages with Interferon-γ Promotes Antioxidant Defenses via the Nrf2-ARE Pathway

Journal of Clinical & Cellular Immunology
Bashar S StaitiehDavid M Guidot

Abstract

Macrophage phenotype and function is dependent on the underlying microenvironment. Many diseases are accompanied by abnormal shifts in macrophage polarization state that limit the ability of the cells to become innate immune effectors. Previous work in the field suggests that chronic alcohol ingestion, which is associated with a shift away from innate immune effector macrophages, is also associated with a deficient response to oxidative stress. We therefore hypothesized that the optimal response to oxidative stress was dependent on the ability of the macrophage to become an innate immune effector cell. To investigate this hypothesis, we first confirmed that we could reproducibly polarize NR8383 cells (a rat alveolar macrophage cell line) into the prototypical M1 and M2 states (using IFN-γ and IL-4, respectively). We then tested the polarized cells for their ability to scavenge reactive oxygen species generated by glucose oxidase (GOX) using the Amplex red assay and found that IFN-γ-polarized cells had greater scavenging capacity. To elucidate the mechanism of the enhanced response to oxidative stress, we then assessed key components of the anti-oxidant response; specifically, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), ...Continue Reading

Citations

Jul 15, 2020·International Journal of Molecular Sciences·Mélanie M LerouxOlivier Joubert
Dec 13, 2016·Jundishapur Journal of Microbiology·Atefeh Davoudi Vijeh MotlaghHossein Asgarian-Omran
Dec 14, 2021·Frontiers in Immunology·Rama K MallampalliJames D Londino

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Methods Mentioned

BETA
lavage
PCR
transfection
flow cytometry

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GraphPad Prism
Excel
FlowJo
FACSDiva

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