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Molecular and phenotypic distinctions of macrophages in tolerant and susceptible to hypoxia rats

Individual hypoxia tolerance is a major influence on the course and outcome of infectious and inflammatory diseases. Macrophages, which play central roles in systemic inflammatory response and other immunity reactions, are subject to functional activation orchestrated by several transcription factor...

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Autores principales: Dzhalilova, Dzhuliia, Kosyreva, Anna, Lokhonina, Anastasiya, Tsvetkov, Ivan, Vishnyakova, Polina, Makarova, Olga, Fatkhudinov, Timur
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10573310/
https://www.ncbi.nlm.nih.gov/pubmed/37842051
http://dx.doi.org/10.7717/peerj.16052
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author Dzhalilova, Dzhuliia
Kosyreva, Anna
Lokhonina, Anastasiya
Tsvetkov, Ivan
Vishnyakova, Polina
Makarova, Olga
Fatkhudinov, Timur
author_facet Dzhalilova, Dzhuliia
Kosyreva, Anna
Lokhonina, Anastasiya
Tsvetkov, Ivan
Vishnyakova, Polina
Makarova, Olga
Fatkhudinov, Timur
author_sort Dzhalilova, Dzhuliia
collection PubMed
description Individual hypoxia tolerance is a major influence on the course and outcome of infectious and inflammatory diseases. Macrophages, which play central roles in systemic inflammatory response and other immunity reactions, are subject to functional activation orchestrated by several transcription factors including hypoxia inducible factors (HIFs). HIF-1 expression levels and the lipopolysaccharide (LPS)-induced systemic inflammatory response severity have been shown to correlate with hypoxia tolerance. Molecular and functional features of macrophages, depending on the organisms resistance to hypoxia, can determine the severity of the course of infectious and inflammatory diseases, including the systemic inflammatory response. The purpose is the comparative molecular and functional characterization of non-activated and LPS-activated bone marrow-derived macrophages under normoxia in rats with different tolerance to oxygen deprivation. Hypoxia resistance was assessed by gasping time measurement in an 11,500 m altitude-equivalent hypobaric decompression chamber. Based on the outcome, the animals were assigned to three groups termed ‘tolerant to hypoxia’ (n = 12), ‘normal’, and ‘susceptible to hypoxia’ (n = 13). The ‘normal’ group was excluded from subsequent experiments. One month after hypoxia resistance test, the blood was collected from the tail vein to isolate monocytes. Non-activated and LPS-activated macrophage cultures were investigated by PCR, flow cytometry and Western blot methods. Gene expression patterns of non-activated cultured macrophages from tolerant and susceptible to hypoxia animals differed. We observed higher expression of VEGF and CD11b and lower expression of Tnfa, Il1b and Epas1 in non-activated cultures obtained from tolerant to hypoxia animals, whereas HIF-1α mRNA and protein expression levels were similar. LPS-activated macrophage cultures derived from susceptible to hypoxia animals expressed higher levels of Hif1a and CCR7 than the tolerant group; in addition, the activation was associated with increased content of HIF-1α in cell culture medium. The observed differences indicate a specific propensity toward pro-inflammatory macrophage polarization in susceptible to hypoxia rats.
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spelling pubmed-105733102023-10-14 Molecular and phenotypic distinctions of macrophages in tolerant and susceptible to hypoxia rats Dzhalilova, Dzhuliia Kosyreva, Anna Lokhonina, Anastasiya Tsvetkov, Ivan Vishnyakova, Polina Makarova, Olga Fatkhudinov, Timur PeerJ Biochemistry Individual hypoxia tolerance is a major influence on the course and outcome of infectious and inflammatory diseases. Macrophages, which play central roles in systemic inflammatory response and other immunity reactions, are subject to functional activation orchestrated by several transcription factors including hypoxia inducible factors (HIFs). HIF-1 expression levels and the lipopolysaccharide (LPS)-induced systemic inflammatory response severity have been shown to correlate with hypoxia tolerance. Molecular and functional features of macrophages, depending on the organisms resistance to hypoxia, can determine the severity of the course of infectious and inflammatory diseases, including the systemic inflammatory response. The purpose is the comparative molecular and functional characterization of non-activated and LPS-activated bone marrow-derived macrophages under normoxia in rats with different tolerance to oxygen deprivation. Hypoxia resistance was assessed by gasping time measurement in an 11,500 m altitude-equivalent hypobaric decompression chamber. Based on the outcome, the animals were assigned to three groups termed ‘tolerant to hypoxia’ (n = 12), ‘normal’, and ‘susceptible to hypoxia’ (n = 13). The ‘normal’ group was excluded from subsequent experiments. One month after hypoxia resistance test, the blood was collected from the tail vein to isolate monocytes. Non-activated and LPS-activated macrophage cultures were investigated by PCR, flow cytometry and Western blot methods. Gene expression patterns of non-activated cultured macrophages from tolerant and susceptible to hypoxia animals differed. We observed higher expression of VEGF and CD11b and lower expression of Tnfa, Il1b and Epas1 in non-activated cultures obtained from tolerant to hypoxia animals, whereas HIF-1α mRNA and protein expression levels were similar. LPS-activated macrophage cultures derived from susceptible to hypoxia animals expressed higher levels of Hif1a and CCR7 than the tolerant group; in addition, the activation was associated with increased content of HIF-1α in cell culture medium. The observed differences indicate a specific propensity toward pro-inflammatory macrophage polarization in susceptible to hypoxia rats. PeerJ Inc. 2023-10-10 /pmc/articles/PMC10573310/ /pubmed/37842051 http://dx.doi.org/10.7717/peerj.16052 Text en ©2023 Dzhalilova et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Biochemistry
Dzhalilova, Dzhuliia
Kosyreva, Anna
Lokhonina, Anastasiya
Tsvetkov, Ivan
Vishnyakova, Polina
Makarova, Olga
Fatkhudinov, Timur
Molecular and phenotypic distinctions of macrophages in tolerant and susceptible to hypoxia rats
title Molecular and phenotypic distinctions of macrophages in tolerant and susceptible to hypoxia rats
title_full Molecular and phenotypic distinctions of macrophages in tolerant and susceptible to hypoxia rats
title_fullStr Molecular and phenotypic distinctions of macrophages in tolerant and susceptible to hypoxia rats
title_full_unstemmed Molecular and phenotypic distinctions of macrophages in tolerant and susceptible to hypoxia rats
title_short Molecular and phenotypic distinctions of macrophages in tolerant and susceptible to hypoxia rats
title_sort molecular and phenotypic distinctions of macrophages in tolerant and susceptible to hypoxia rats
topic Biochemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10573310/
https://www.ncbi.nlm.nih.gov/pubmed/37842051
http://dx.doi.org/10.7717/peerj.16052
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