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Lee-Kwon, Whaseon
School of Life Science
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  • Calcium signalling in cancer cell

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TonEBP suppresses IL-10-mediated immunomodulation

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Title
TonEBP suppresses IL-10-mediated immunomodulation
Author
Choi, Soo YounLee, Hwan HeeLee, Jun HoYe, Byeong JinYoo, Eun JinKang, Hyun JeJung, Gyu WonAn, Seung MinLee-Kwon, WhaseonChiong, MarioLavandero, SergioKwon, H. Moo
Keywords
TONICITY-RESPONSIVE ENHANCER; TRANSCRIPTION FACTOR NFAT5; MACROPHAGE ACTIVATION; NUCLEAR-FACTOR; INSULIN-RESISTANCE; IL-10; CELLS; GENE; INTERLEUKIN-10; POLARIZATION
Issue Date
201605
Publisher
NATURE PUBLISHING GROUP
Citation
SCIENTIFIC REPORTS, v.6, no., pp.25726 -
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
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DOI
http://dx.doi.org/10.1038/srep25726
ISSN
2045-2322
Appears in Collections:
SLS_Journal Papers
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