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

Hongwei Wang, Fengdong Cheng, Karrune Woan, Eva Sahakian, Oscar Merino, Jennifer Rock-Klotz, Ildefonso Vicente-Suarez, Javier Pinilla-Ibarz, Kenneth L. Wright, Edward Seto, Kapil Bhalla, Alejandro Villagra, Eduardo M. Sotomayor

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3986-3996
Number of pages11
JournalJournal of Immunology
Volume186
Issue number7
DOIs
StatePublished - Apr 1 2011

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