title: [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.affiliation: Ministry-of-Education Key Laboratory of Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016; Department of Clinical Laboratory, Bishan County People's Hospital, Chongqing 402760, China.
authors.forename: Changli
authors.initials: C
authors.lastname: Xie
authors.affiliation: Ministry-of-Education Key Laboratory of Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Bianqin
authors.initials: B
authors.lastname: Guo
authors.affiliation: Ministry-of-Education Key Laboratory of Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Cuiying
authors.initials: C
authors.lastname: Liu
authors.affiliation: Ministry-of-Education Key Laboratory of Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Ministry-of-Education Key Laboratory of Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Bitao
authors.initials: B
authors.lastname: Wu
authors.affiliation: Ministry-of-Education Key Laboratory of Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Ministry-of-Education Key Laboratory of Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: Ministry-of-Education Key Laboratory of Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. *Corresponding author, E-mail: tuzhiguang@aliyun.com.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Tu
mesh_terms: D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005434:Flow Cytometry; D056945:Hep G2 Cells; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology; D008262:Macrophage Activation; D008264:Macrophages / Q000145:classification / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D020298:U937 Cells
chemical_list: D017077:Culture Media, Conditioned; C431713:IRF5 protein, human; D050856:Interferon Regulatory Factor-1; D050835:Interferon Regulatory Factors; D053759:Interleukin-23; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D016899:Interferon-beta