Open AccessHistone deacetylase 5 regulates the inflammatory response of macrophages
Author(s) -
Poralla Lukas,
Stroh Thorsten,
Erben Ulrike,
Sittig Marie,
Liebig Sven,
Siegmund Britta,
Glauben Rainer
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12595
Subject(s) - histone deacetylase 5 , histone deacetylase , biology , microbiology and biotechnology , chromatin immunoprecipitation , transcription factor , cytokine , tumor necrosis factor alpha , histone , immunology , gene expression , biochemistry , promoter , gene
Modifying the chromatin structure and interacting with non‐histone proteins, histone deacetylases ( HDAC ) are involved in vital cellular processes at different levels. We here specifically investigated the direct effects of HDAC 5 in macrophage activation in response to bacterial or cytokine stimuli. Using murine and human macrophage cell lines, we studied the expression profile and the immunological function of HDAC 5 at transcription and protein level in over‐expression as well as RNA interference experiments. Toll‐like receptor‐mediated stimulation of murine RAW 264.7 cells significantly reduced HDAC 5 mRNA within 7 hrs but presented baseline levels after 24 hrs, a mechanism that was also found for Interferon‐γ treatment. If treated with lipopolysaccharide, RAW 264.7 cells transfected for over‐expression only of full‐length but not of mutant HDAC 5, significantly elevated secretion of tumour necrosis factor α and of the monocyte chemotactic protein‐1. These effects were accompanied by increased nuclear factor‐κB activity. Accordingly, knock down of HDAC 5‐ mRNA expression using specific si RNA significantly reduced the production of these cytokines in RAW 264.7 or human U937 cells. Taken together, our results suggest a strong regulatory function of HDAC 5 in the pro‐inflammatory response of macrophages.