Cycling hypoxia promotes a pro-inflammatory phenotype in macrophages via JNK/p65 signaling pathway

Victor Delprat, Céline Tellier, Catherine Demazy, Martine Raes, Olivier Feron, Carine Michiels

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)882
Number of pages13
JournalScientific Reports
Volume10
Issue number1
DOIs
Publication statusPublished - 2020
Externally publishedYes

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MAP Kinase Signaling System
Macrophages
Phenotype
Hypoxia
Neoplasms
Tumor Microenvironment
Interleukin-8

Cite this

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title = "Cycling hypoxia promotes a pro-inflammatory phenotype in macrophages via JNK/p65 signaling pathway",
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.",
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Cycling hypoxia promotes a pro-inflammatory phenotype in macrophages via JNK/p65 signaling pathway. / Delprat, Victor; Tellier, Céline; Demazy, Catherine; Raes, Martine; Feron, Olivier; Michiels, Carine.

In: Scientific Reports, Vol. 10, No. 1, 2020, p. 882.

Research output: Contribution to journalArticle

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AU - Tellier, Céline

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AU - Raes, Martine

AU - Feron, Olivier

AU - Michiels, Carine

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