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PMID: 21368229 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Histone deacetylase inhibitor LAQ824 augments inflammatory responses in macrophages through transcriptional regulation of IL-10.

Journal of immunology (Baltimore, Md. : 1950) ·Vol. 186 ·No. 7 ·2011-04-01 ·Pages 3986-96

Wang H, Cheng F, Woan K, Sahakian E, Merino O, Rock-Klotz J, Vicente-Suarez I, Pinilla-Ibarz J, Wright KL, Seto E, Bhalla K, Villagra A, Sotomayor EM

Abstract

APCs are important in the initiation of productive Ag-specific T cell responses and the induction of T cell anergy. The inflammatory status of the APC at the time of encounter with Ag-specific T cells plays a central role in determining such divergent T cell outcomes. A better understanding of the regulation of proinflammatory and anti-inflammatory genes in its natural setting, the chromatin substrate, might provide novel insights to overcome anergic mechanisms mediated by APCs. In this study, we show for the first time, to our knowledge, that treatment of BALB/c murine macrophages with the histone deacetylase inhibitor LAQ824 induces chromatin changes at the level of the IL-10 gene promoter that lead to enhanced recruitment of the transcriptional repressors HDAC11 and PU.1. Such an effect is associated with diminished IL-10 production and induction of inflammatory cells able of priming naive Ag-specific T cells, but more importantly, capable of restoring the responsiveness of anergized Ag-specific CD4(+) T cells.

MeSH Terms
Adjuvants, Immunologic/pharmacology Animals Cell Line Cell Line, Tumor Histone Deacetylase Inhibitors/pharmacology Hydroxamic Acids/pharmacology Indoles Inflammation Mediators/pharmacology Interleukin-10/antagonists & inhibitors,genetics,metabolism Macrophages, Peritoneal/drug effects,enzymology,immunology Male Mice Mice, Inbred BALB C Mice, Transgenic Panobinostat Spleen/cytology,enzymology,immunology Transcription, Genetic/drug effects,immunology
Chemicals
Adjuvants, Immunologic Histone Deacetylase Inhibitors Hydroxamic Acids IL10 protein, mouse Indoles Inflammation Mediators LAQ824 Interleukin-10 Panobinostat
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Wang Hongwei
Department of Immunology and Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL 33613, USA.
Cheng Fengdong
Woan Karrune
Sahakian Eva
Merino Oscar
Rock-Klotz Jennifer
Vicente-Suarez Ildefonso
Pinilla-Ibarz Javier
Wright Kenneth L
Seto Edward
Bhalla Kapil
Villagra Alejandro
Sotomayor Eduardo M
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Article Info
Journal
Journal of immunology (Baltimore, Md. : 1950)
Abbr.
J Immunol
ISSN
1550-6606
DOI
10.4049/jimmunol.1001101
Published
2011-04-01
Epub
2011-00-02
Pages
3986-96
Language
English
Region
United States
NLM ID
2985117R
PMCID
PMC3998678
Subset
IM
Grants
NCI NIH HHS · R01 CA087583 · United States
NCI NIH HHS · CA87583 · United States
NCI NIH HHS · P30 CA076292 · United States
NCI NIH HHS · R01 CA134807 · United States
NCI NIH HHS · R01 CA100850 · United States
NCI NIH HHS · CA134807 · United States
External Links
PubMed source DOI: 10.4049/jimmunol.1001101 PMC Full Text View journal details
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