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Molecular Mechanisms Regulating Macrophage Response to Hypoxia

Monocytes and Macrophages (Mo/Mɸ) exhibit great plasticity, as they can shift between different modes of activation and, driven by their immediate microenvironment, perform divergent functions. These include, among others, patrolling their surroundings and maintaining homeostasis (resident Mo/Mɸ), c...

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Autores principales: Rahat, Michal A., Bitterman, Haim, Lahat, Nitza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Research Foundation 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342364/
https://www.ncbi.nlm.nih.gov/pubmed/22566835
http://dx.doi.org/10.3389/fimmu.2011.00045
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author Rahat, Michal A.
Bitterman, Haim
Lahat, Nitza
author_facet Rahat, Michal A.
Bitterman, Haim
Lahat, Nitza
author_sort Rahat, Michal A.
collection PubMed
description Monocytes and Macrophages (Mo/Mɸ) exhibit great plasticity, as they can shift between different modes of activation and, driven by their immediate microenvironment, perform divergent functions. These include, among others, patrolling their surroundings and maintaining homeostasis (resident Mo/Mɸ), combating invading pathogens and tumor cells (classically activated or M1 Mo/Mɸ), orchestrating wound healing (alternatively activated or M2 Mo/Mɸ), and restoring homeostasis after an inflammatory response (resolution Mɸ). Hypoxia is an important factor in the Mɸ microenvironment, is prevalent in many physiological and pathological conditions, and is interdependent with the inflammatory response. Although Mo/Mɸ have been studied in hypoxia, the mechanisms by which hypoxia influences the different modes of their activation, and how it regulates the shift between them, remain unclear. Here we review the current knowledge about the molecular mechanisms that mediate this hypoxic regulation of Mɸ activation. Much is known about the hypoxic transcriptional regulatory network, which includes the master regulators hypoxia-induced factor-1 and NF-κB, as well as other transcription factors (e.g., AP-1, Erg-1), but we also highlight the role of post-transcriptional and post-translational mechanisms. These mechanisms mediate hypoxic induction of Mɸ pro-angiogenic mediators, suppress M1 Mɸ by post-transcriptionally inhibiting pro-inflammatory mediators, and help shift the classically activated Mɸ into an activation state which approximate the alternatively activated or resolution Mɸ.
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spelling pubmed-33423642012-05-07 Molecular Mechanisms Regulating Macrophage Response to Hypoxia Rahat, Michal A. Bitterman, Haim Lahat, Nitza Front Immunol Immunology Monocytes and Macrophages (Mo/Mɸ) exhibit great plasticity, as they can shift between different modes of activation and, driven by their immediate microenvironment, perform divergent functions. These include, among others, patrolling their surroundings and maintaining homeostasis (resident Mo/Mɸ), combating invading pathogens and tumor cells (classically activated or M1 Mo/Mɸ), orchestrating wound healing (alternatively activated or M2 Mo/Mɸ), and restoring homeostasis after an inflammatory response (resolution Mɸ). Hypoxia is an important factor in the Mɸ microenvironment, is prevalent in many physiological and pathological conditions, and is interdependent with the inflammatory response. Although Mo/Mɸ have been studied in hypoxia, the mechanisms by which hypoxia influences the different modes of their activation, and how it regulates the shift between them, remain unclear. Here we review the current knowledge about the molecular mechanisms that mediate this hypoxic regulation of Mɸ activation. Much is known about the hypoxic transcriptional regulatory network, which includes the master regulators hypoxia-induced factor-1 and NF-κB, as well as other transcription factors (e.g., AP-1, Erg-1), but we also highlight the role of post-transcriptional and post-translational mechanisms. These mechanisms mediate hypoxic induction of Mɸ pro-angiogenic mediators, suppress M1 Mɸ by post-transcriptionally inhibiting pro-inflammatory mediators, and help shift the classically activated Mɸ into an activation state which approximate the alternatively activated or resolution Mɸ. Frontiers Research Foundation 2011-09-16 /pmc/articles/PMC3342364/ /pubmed/22566835 http://dx.doi.org/10.3389/fimmu.2011.00045 Text en Copyright © 2011 Rahat, Bitterman and Lahat. http://www.frontiersin.org/licenseagreement This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.
spellingShingle Immunology
Rahat, Michal A.
Bitterman, Haim
Lahat, Nitza
Molecular Mechanisms Regulating Macrophage Response to Hypoxia
title Molecular Mechanisms Regulating Macrophage Response to Hypoxia
title_full Molecular Mechanisms Regulating Macrophage Response to Hypoxia
title_fullStr Molecular Mechanisms Regulating Macrophage Response to Hypoxia
title_full_unstemmed Molecular Mechanisms Regulating Macrophage Response to Hypoxia
title_short Molecular Mechanisms Regulating Macrophage Response to Hypoxia
title_sort molecular mechanisms regulating macrophage response to hypoxia
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342364/
https://www.ncbi.nlm.nih.gov/pubmed/22566835
http://dx.doi.org/10.3389/fimmu.2011.00045
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