title: TonEBP suppresses IL-10-mediated immunomodulation.
abstract: TonEBP is a key transcriptional activator of M1 phenotype in macrophage, and its high expression is associated with many inflammatory diseases. During the progression of the inflammatory responses, the M1 to M2 phenotypic switch enables the dual role of macrophages in controlling the initiation and resolution of inflammation. Here we report that in human and mouse M1 macrophages TonEBP suppresses IL-10 expression and M2 phenotype. TonEBP knockdown promoted the transcription of the IL-10 gene by enhancing chromatin accessibility and Sp1 recruitment to its promoter. The enhanced expression of M2 genes by TonEBP knockdown was abrogated by antagonism of IL-10 by either neutralizing antibodies or siRNA-mediated silencing. In addition, pharmacological suppression of TonEBP leads to similar upregulation of IL-10 and M2 genes. Thus, TonEBP suppresses M2 phenotype via downregulation of the IL-10 in M1 macrophages.
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
authors.forename: Soo Youn
authors.initials: SY
authors.lastname: Choi
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
authors.forename: Hwan Hee
authors.initials: HH
authors.lastname: Lee
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
authors.forename: Byeong Jin
authors.initials: BJ
authors.lastname: Ye
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Yoo
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
authors.forename: Hyun Je
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
authors.forename: Gyu Won
authors.initials: GW
authors.lastname: Jung
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
authors.forename: Seung Min
authors.initials: SM
authors.lastname: An
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
authors.forename: Whaseon
authors.initials: W
authors.lastname: Lee-Kwon
authors.affiliation: Advanced Center for Chronic Disease (ACCDiS) &Center for Molecular Studies of the Cell, Facultad Ciencias Quimicasy Farmaceuticas &Facultad Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Mario
authors.initials: M
authors.lastname: Chiong
authors.affiliation: Advanced Center for Chronic Disease (ACCDiS) &Center for Molecular Studies of the Cell, Facultad Ciencias Quimicasy Farmaceuticas &Facultad Medicina, Universidad de Chile, Santiago, Chile.|Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Sergio
authors.initials: S
authors.lastname: Lavandero
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
authors.forename: Hyug Moo
authors.initials: HM
authors.lastname: Kwon
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002843:Chromatin / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D009285:Naphthoquinones / Q000494:pharmacology; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014019:Tissue Donors; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002843:Chromatin; D050778:NFATC Transcription Factors; D009285:Naphthoquinones; D016329:Sp1 Transcription Factor; D016753:Interleukin-10; D015847:Interleukin-4; C014638:beta-lapachone