title: Lithium chloride suppresses LPS-mediated matrix metalloproteinase-9 expression in macrophages through phosphorylation of GSK-3β.
abstract: 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.
authors: Laboratory of Genome to Drug Medicine, Joint Center for Biosciences, 7-45 Songdo-dong, Yeonsu-ku, Incheon, Korea.
authors: Sooho
authors: S
authors: Kim
authors: Naeun
authors: N
authors: Bong
authors: Ok Soo
authors: OS
authors: Kim
authors: JunYup
authors: J
authors: Jin
authors: Dong-Eog
authors: DE
authors: Kim
authors: Dong Kun
authors: DK
authors: Lee
mesh_terms: D000107:Acetylation; D000818:Animals; D002460:Cell Line; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006657:Histones / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D018021:Lithium Chloride / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: C473711:Chir 99021; D006657:Histones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011725:Pyridines; D011743:Pyrimidines; D018808:Transcription Factor AP-1; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D020780:Matrix Metalloproteinase 9; D018021:Lithium Chloride
keywords: GSK-3β; HDAC; MMP-9; lipopolysaccharide; macrophage