[Endogenous IFN-β maintains M1 polarization status and inhibits proliferation and invasion of hepatocellular carcinoma cells].

Abstract

Objective To investigate the effect of endogenous interferon β (IFN-β) on the polarization of M1 macrophages as well as the proliferation and invasion activities of hepatocellular carcinoma cells (HCCs) mediated by M1 macrophages. Methods U937-M1 macrophages derived from human monocytic tumor cells U937 was established and the cell phenotypes were identified by real-time quantitative PCR, ELISA and flow cytometry. After IFN-β gene was knocked down with siRNA or IFN-β was neutralized with IFN-β monoantibody in U937-M1 macrophages, the change of M1/M2 phenotype was again analyzed by the above methods. The expressions of interferon regulatory factor 1 (IRF1) and IRF5 were detected by real-time quantitative PCR and Western blotting. The proliferation and invasion activities of HCCs, which were cultured with conditioned medium (CM) collected from different macrophage groups, were analyzed by CCK-8 assay and Transwell(TM) experiments, respectively. Results U937-M1 macrophages showed higher expressions of interleukin 12p35 (IL-12p35), interleukin 12p40 (IL-12p40), interleukin 12p70 (IL-12p70), interleukin 23p19 (IL-23p19), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and CD86 than U937-M0 did. But both U937-M0 macrophages and U937-M1 macrophages showed low expression of CD206. However, compared with the U937-M1 macrophages, the IFN-β-blocked U937-M1 macrophages presented decreased expressions of the above M1 macrophages-associated markers, but increased expressions of M2 macrophages-associated markers IL-10 and CD206, as well as lower expressions of IRF1 and IRF5. The inhibited proliferation/invasion activities of HCCs mediated by U937-M1 macrophages were reversed by IFN-β-blocked U937-M1 macrophages. Conclusion Blocking endogenous IFN-β could inhibit the U937-M1 polarization status and U937-M1 macrophages-mediated anti-tumor activity of HCCs. IFN-β might be involved in modulating the expressions of IRF1 and IRF5 as well as maintaining the M1 polarization status and its function.

• Authors: Changli Xie, Bianqin Guo, Cuiying Liu, Yan Lin, Bitao Wu, Qin Wang, Ziwei Li, Zhiguang Tu
• Journal: Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology (Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi) Vol. 32 Issue 7 Pg. 865-9 (Jul 2016) ISSN: 1007-8738 [Print] China
• PMID: 27363262 (Publication Type: Journal Article)

Chemical References

• Culture Media, Conditioned
• IRF5 protein, human
• Interferon Regulatory Factor-1
• Interferon Regulatory Factors
• Interleukin-23
• Lectins, C-Type
• Mannose Receptor
• Mannose-Binding Lectins
• Receptors, Cell Surface
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Interleukin-12
• Interferon-beta

Topics

• Blotting, Western
• Carcinoma, Hepatocellular (pathology)
• Cell Line, Tumor
• Cell Proliferation
• Cell Survival (drug effects)
• Culture Media, Conditioned (pharmacology)
• Flow Cytometry
• Hep G2 Cells
• Humans
• Interferon Regulatory Factor-1 (genetics, metabolism)
• Interferon Regulatory Factors (genetics, metabolism)
• Interferon-beta (genetics, metabolism)
• Interleukin-10 (genetics, metabolism)
• Interleukin-12 (genetics, metabolism)
• Interleukin-23 (genetics, metabolism)
• Lectins, C-Type (genetics, metabolism)
• Liver Neoplasms (pathology)
• Macrophage Activation
• Macrophages (classification, metabolism)
• Mannose Receptor
• Mannose-Binding Lectins (genetics, metabolism)
• Neoplasm Invasiveness
• RNA Interference
• Receptors, Cell Surface (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Necrosis Factor-alpha (genetics, metabolism)
• U937 Cells