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Histone deacetylase 3 mediates allergic skin inflammation by regulating expression of MCP1 protein

Title
Histone deacetylase 3 mediates allergic skin inflammation by regulating expression of MCP1 protein
Authors
Kim Y.Kim K.Park D.Lee E.Lee H.Lee Y.-S.Choe J.Jeoung D.
Ewha Authors
이윤실
SCOPUS Author ID
이윤실scopus
Issue Date
2012
Journal Title
Journal of Biological Chemistry
ISSN
0021-9258JCR Link
Citation
vol. 287, no. 31, pp. 25844 - 25859
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
We have shown the induction of histone deacetylase 3 (HDAC3) in antigen-stimulated rat basophilic leukemia cells via NF-κB. We investigated the role of HDAC3 in allergic skin inflammation. We used a BALB/c mouse model of triphasic cutaneous anaphylaxis (triphasic cutaneous reaction; TpCR) and passive cutaneous anaphylaxis (PCA) to examine the role of HDAC3 in allergic skin inflammation. Triphasic cutaneous reaction involved induction of HDAC3 and was mediated by HDAC3. HDAC3 showed an interaction with FcεRIβ. Trichostatin A (TSA), an inhibitor of HDAC(s), disrupted this interaction. Cytokine array analysis showed that the down-regulation of HDAC3 led to the decreased secretion of monocyte chemoattractant protein 1 (MCP1). FcεRI was necessary for induction of HDAC3 and MCP1. ChIP assays showed that HDAC3, in association with Sp1 and c-Jun, was responsible for induction of MCP1 expression. TSA exerted a negative effect on induction of MCP1. HDAC3 exerted a negative regulation on expression of HDAC2 via interaction with Rac1. The down-regulation of HDAC3 or inactivation of Rac1 induced binding of HDAC2 to MCP1 promoter sequences. TSA exerted a negative effect on HDAC3-mediated TpCR. The BALB/c mouse model of PCA involved induction of HDAC3 and MCP1. HDAC3 and MCP1 were necessary for PCA that involved ear swelling, enhanced vascular permeability, and angiogenesis. Recombinant MCP1 enhanced β-hexosaminidase activity and histamine release and also showed angiogenic potential. TSA exerted a negative effect on PCA. Our data show HDAC3 as a valuable target for the development of allergic skin inflammation therapeutics. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
DOI
10.1074/jbc.M112.348284
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약학대학 > 약학과 > Journal papers
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