title: TGF-β induces M2-like macrophage polarization via SNAIL-mediated suppression of a pro-inflammatory phenotype.
abstract: Tumor-associated macrophages (TAMs) are a major component of leukocytic infiltrate in tumors, which facilitates tumor progression and promotes inflammation. TGF-β promotes the differentiation of non-activated macrophages into a TAM-like (M2-like) phenotype; however, the underlying mechanisms are not clear. In this study, we found that TGF-β induces a M2-like phenotype characterized by up-regulation of the anti-inflammatory cytokine IL-10, and down-regulation of the pro-inflammatory cytokines TNF-α and IL-12. In human THP-1 macrophages, overexpression of SNAIL caused M2-like differentiation by inhibiting pro-inflammatory cytokine release and promoting the expression of M2-specific markers. By contrast, SNAIL knockdown promoted M1 polarization through up-regulation of pro-inflammatory cytokines and abolished TGF-β-mediated M2-polarization of THP-1 macrophages. The SMAD2/3 and PI3K/AKT signaling pathways were crucial for TGF-β-induced SNAIL overexpression in THP-1 cells. These findings suggest that TGF-β skews macrophage polarization towards a M2-like phenotype via SNAIL up-regulation, and blockade of TGF-β/SNAIL signaling restores the production of pro-inflammatory cytokines. This study provides new understanding of the role of SNAIL in M2 polarization of macrophages, and suggests a potential therapeutic target for antitumor immunity.
authors.affiliation: Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, PR China.|Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Shijiazhuang City Center for Disease Control and Prevention, Shijiazhuang 050000, PR China.
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, PR China.
authors.forename: Guanmin
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Cancer Hospital and Cancer Research Institute, Guangzhou Medical University, Guangzhou 510095, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Fang
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Xianzhang
authors.initials: X
authors.lastname: Bu
authors.affiliation: Department of Pharmacology, College of Pharmacy, Jinan University, Guangzhou 510632, PR China.
authors.forename: Shaohui
authors.initials: S
authors.lastname: Cai
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Du
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D045744:Cell Line, Tumor; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D000071250:Snail Family Transcription Factors / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000378:metabolism
chemical_list: D000071250:Snail Family Transcription Factors; D016212:Transforming Growth Factor beta
keywords: SNAIL; TGF-β; immunotherapy; macrophage polarization; tumor-associated macrophage