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GSK 3 β Negatively Regulates LPS ‐induced Osteopontin Expression via Inhibiting its Transcription
Author(s) -
Song H.,
Deng B.,
Zou C.,
Huai W.,
Zhao R.,
Zhao W.
Publication year - 2015
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12268
Subject(s) - osteopontin , gsk 3 , immune system , microbiology and biotechnology , innate immune system , chemistry , regulator , downregulation and upregulation , biology , phosphorylation , cancer research , immunology , biochemistry , gene
Osteopontin ( OPN ) is expressed by a variety of immune cells and is critical for both innate and adaptive immune responses. The expression status of OPN might be tightly regulated to maintain immune homeostasis. However, the mechanisms by which OPN is negatively regulated in LPS ‐stimulated macrophages remain largely unknown. In this study, we showed that glycogen synthase kinase 3 β ( GSK 3 β ) inhibitors – SB 216763, LiCl and azakenpaullone – enhanced LPS ‐induced OPN expression in mouse peritoneal macrophages. GSK 3 β knock‐down had the similar effects. Furthermore, we found that GSK 3 β inhibitors and GSK 3 β knock‐down both increased the activity of OPN promoter in LPS ‐stimulated macrophages. GSK 3 β inhibitor‐mediated enhancement of LPS ‐induced OPN promoter activity was abrogated in GSK 3 β si RNA ‐treated macrophages. Therefore, we identified GSK 3 β as a negative regulator of OPN expression and suggest GSK 3 β as a potential therapeutic target for the intervention of diseases with uncontrolled OPN production.