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Lithium chloride suppresses LPS‐mediated matrix metalloproteinase‐9 expression in macrophages through phosphorylation of GSK‐3β
Author(s) -
Kim Sooho,
Bong Naeun,
Kim Ok Soo,
Jin JunYup,
Kim DongEog,
Lee Dong Kun
Publication year - 2015
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10352
Subject(s) - lithium chloride , chemistry , phosphorylation , gsk 3 , matrix metalloproteinase , gsk3b , downregulation and upregulation , glycogen synthase , kinase , microbiology and biotechnology , signal transduction , cancer research , biochemistry , gene , biology , organic chemistry
Abnormal degradation of matrix components due to dysregulated expression of matrix metalloproteinase (MMP)‐9 in macrophages has been linked to progression of acute cerebral ischemia and atherosclerosis. We report that lithium chloride (LiCl) or CHIR99021, inhibitors of Wnt signaling pathway, enhance phosphorylation of glycogen synthase kinase‐3beta and suppress lipopolysaccharide‐mediated upregulation of MMP‐9 expression in murine macrophage RAW264.7 cells in a dose‐dependent manner. Suppression of MMP‐9 expression by LiCl or CHIR99021 did not result after inhibition of kinases involved in NFκB or AP‐1 family proteins, but from changes in the activity of histone deacetylases. Beneficial effects on atherosclerosis or cerebral ischemia in animal studies caused by LiCl may be in part explained by the suppression of MMP‐9 gene expression.