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LPS regulates proinflammatory gene expression in macrophages by altering histone deacetylase expression
Author(s) -
Aung Hnin Thanda,
Schroder Kate,
Himes Stewart R.,
Brion Kristian,
Van Zuylen Wendy,
Trieu Angela,
Suzuki Harukazu,
Hayashizaki Yoshihide,
Hume David A.,
Sweet Matthew J.,
Ravasi Timothy
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-5360com
Subject(s) - trichostatin a , histone deacetylase , proinflammatory cytokine , hdac11 , gene expression , chemistry , lipopolysaccharide , histone deacetylase 2 , microbiology and biotechnology , cxcl2 , regulation of gene expression , histone deacetylase 5 , histone deacetylase inhibitor , hdac1 , messenger rna , histone , gene , biology , inflammation , chemokine , immunology , biochemistry , chemokine receptor
Bacterial LPS triggers dramatic changes in gene expression in macrophages. We show here that LPS regulated several members of the histone deacetylase (HDAC) family at the mRNA level in murine bone marrow‐derived macrophages (BMM). LPS transiently repressed, then induced a number of HDACs ( Hdac‐4, 5, 7 ) in BMM, whereas Hdac‐1 mRNA was induced more rapidly. Treatment of BMM with trichostatin A (TSA), an inhibitor of HDACs, enhanced LPS‐induced expression of the Cox‐2, Cxcl2 , and Ifit2 genes. In the case of Cox‐2 , this effect was also apparent at the promoter level. Overexpression of Hdac‐8 in RAW264 murine macrophages blocked the ability of LPS to induce Cox‐2 mRNA. Another class of LPS‐inducible genes, which included Ccl2, Ccl7 , and Edn1 , was suppressed by TSA, an effect most likely mediated by PU.1 degradation. Hence, HDACs act as potent and selective negative regulators of proinflammatory gene expression and act to prevent excessive inflammatory responses in macrophages.—Aung, H. T., Schroder, K., Himes, S. R., Brion, K., van Zuylen, W., Trieu, A., Suzuki, H., Hayashizaki, Y., Hume, D. A., Sweet, M. J., Ravasi, T. LPS regulates proinflammatory gene expression in macrophages by altering histone deacetylase expression. FASEB J. 20, 1315–1327 (2006)