Effects of IRF1 and IFN-β interaction on the M1 polarization of macrophages and its antitumor function

Xie,Changli; Liu,Cuiying; Wu,Bitao; Lin,Yan; Ma,Tingting; Xiong,Haiyu; Wang,Qin; Li,Ziwei; Ma,Chenyu; Tu,Zhiguang

doi:10.3892/ijmm.2016.2583

Effects of IRF1 and IFN-β interaction on the M1 polarization of macrophages and its antitumor function

Authors:
- Changli Xie
- Cuiying Liu
- Bitao Wu
- Yan Lin
- Tingting Ma
- Haiyu Xiong
- Qin Wang
- Ziwei Li
- Chenyu Ma
- Zhiguang Tu
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Affiliations: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China
Published online on: May 10, 2016 https://doi.org/10.3892/ijmm.2016.2583
Pages: 148-160
Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Macrophages that differentiate from precursor monocytes can be polarized into a classically activated (M1) or alternatively activated (M2) status depending on different stimuli. Generally, interferon (IFN)-γ and lipopolysaccharide (LPS) are considered the classical stimuli with which to establish M1 polarization. IFN regulatory factor (IRF)1 and IFN-β are two crucial molecules involved in IFN-γ- and LPS-initialed signaling. However, the association between IRF1 and IFN-β in the context of the M1 polarization of macrophages is not yet fully understood. In this study, we demonstrate that U937-derived macrophages, in response to IFN-γ and LPS stimulation, readily acquire an M1 status, indicated by the increased expression of interleukin (IL)-12, IL-6, IL-23, tumor necrosis factor (TNF)-α and the M1-specific cell surface antigen, CD86, and the decreased expression of the M2-specific mannose receptor, CD206. However, the knockdown of IRF1 in U937-derived macrophages led to an impaired M1 status, as indicated by the decreased expression of the above-mentioned M1 markers, and the increased expression of the M2 markers, CD206 and IL-10. A similar phenomenon was observed in the M1 macrophages in which IFN-β was inhibited. Furthermore, we demonstrated that IRF1 and IFN-β may interact with each other in the IFN-γ- and LPS-initiated signaling pathway, and contribute to the IRF5 regulation of M1 macrophages. In addition, the conditioned medium collected from the M1 macrophages in which IRF1 or IFN-β were inhibited, exerted pro-tumor effects on the HepG2 and SMMC-7721 cells, as indicated by an increase in proliferation, the inhibition of apoptosis and an enhanced invasion capability. The findings of our study suggest that the interactions of IRF1, IFN-β and IRF5 are involved in the M1 polarization of macrophages and have antitumor functions. These data may provide a novel antitumor strategy for targeted cancer therapy.

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