Abstract
Cycling hypoxia (cyH), also called intermittent hypoxia, occurs in solid tumors and affects different cell types in the tumor microenvironment and in particular the tumor-associated macrophages (TAMs). As cyH and TAMs both favor tumor progression, we investigated whether cyH could drive the pro-tumoral phenotype of macrophages. Here, the effects of cyH on human THP-1 macrophages and murine bone marrow-derived macrophages (BMDM), either unpolarized M0, or polarized in M1 or M2 phenotype were studied. In M0 macrophages, cyH induced a pro-inflammatory phenotype characterized by an increase in TNFα and IL-8/MIP-2 secretion. CyH amplified the pro-inflammatory phenotype of M1 macrophages evidenced by an increased pro-inflammatory cytokine secretion and pro-inflammatory gene expression. Furthermore, cyH increased c-jun activation in human M0 macrophages and highly increased c-jun and NF-κB activation in M1 macrophages. C-jun and p65 are implicated in the effects of cyH on M0 and M1 macrophages since inhibition of their activation prevented the cyH pro-inflammatory effects. In conclusion, we demonstrated that cyH induces or amplifies a pro-inflammatory phenotype in M0 and M1 macrophages by activating JNK/p65 signaling pathway. These results highlight a specific role of cyH in the amplification of tumor-related inflammation by modulating the inflammatory phenotype of macrophages.
Original language | English |
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Article number | 882 |
Pages (from-to) | 882 |
Number of pages | 13 |
Journal | Scientific Reports |
Volume | 10 |
Issue number | 1 |
DOIs | |
Publication status | Published - 21 Jan 2020 |
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Flow Cytometry
Jean-Yves Matroule (Manager) & Kevin Willemart (Other)
Technological Platform Morphology - ImagingFacility/equipment: Equipment
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Light Microscopy
Henri-Francois Renard (Manager), Alison Forrester (Manager), Catherine Demazy (Other) & Benjamin Ledoux (Manager)
Technological Platform Morphology - ImagingFacility/equipment: Equipment
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Morphology - Imaging
Francesca Cecchet (Manager) & Henri-Francois Renard (Manager)
Technological Platform Morphology - ImagingFacility/equipment: Technological Platform
Student theses
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Study of the effects of cycling hypoxia on macrophages and on the interaction between macrophages and endothelial cells: role in the promotion of tumor inflammation
Author: DELPRAT, V., 24 Aug 2021Supervisor: MICHIELS, C. (Supervisor), Gillet, J. (President), Lambert De Rouvroit, C. (Jury), Féron, O. (External person) (Jury), Graux, C. (Jury) & Soncin, F. (External person) (Jury)
Student thesis: Doc types › Doctor of Sciences
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