Panhistone deacetylase inhibitors inhibit proinflammatory signaling pathways to ameliorate interleukin-18-induced cardiac hypertrophy
Autor: | Rajendra Raghow, Gipsy Majumdar, I. Maria Johnson, Robert J. Rooney |
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Jazyk: | angličtina |
Rok vydání: | 2011 |
Předmět: |
MAPK/ERK pathway
Male Physiology Intracellular Space Cardiomegaly Biology Hydroxamic Acids Proinflammatory cytokine Histones Mice Gene expression Genetics medicine Tensin Animals Cluster Analysis Gene Regulatory Networks Oligonucleotide Array Sequence Analysis Regulation of gene expression Inflammation Mice Inbred BALB C Gene Expression Profiling Myocardium Interleukin-18 Reproducibility of Results Chromatin Assembly and Disassembly Molecular biology Call for Papers: Technology Development for Physiological Genomics Cell biology Histone Deacetylase Inhibitors Trichostatin A Gene Expression Regulation Cinnamates Interleukin 18 Signal transduction Protein Processing Post-Translational medicine.drug Signal Transduction |
Popis: | We investigated the genome-wide consequences of pan-histone deacetylase inhibitors (HDACIs) trichostatin A (TSA) and m-carboxycinnamic acid bis-hydroxamide (CBHA) in the hearts of BALB/c mice eliciting hypertrophy in response to interleukin-18 (IL-18). Both TSA and CBHA profoundly altered cardiac chromatin structure that occurred concomitantly with normalization of IL-18-induced gene expression and amelioration of cardiac hypertrophy. The hearts of mice exposed to IL-18 +/− TSA or CBHA elicited distinct gene expression profiles. Of 184 genes that were differentially regulated by IL-18 and TSA, 33 were regulated in an opposite manner. The hearts of mice treated with IL-18 and/or CBHA elicited 147 differentially expressed genes (DEGs), a third of which were oppositely regulated by IL-18 and CBHA. Ingenuity Pathways and Kyoto Encyclopedia of Genes and Genomes analyses of DEGs showed that IL-18 impinged on TNF-α- and IFNγ-specific gene networks relegated to controlling immunity and inflammation, cardiac metabolism and energetics, and cell proliferation and apoptosis. These TNF-α- and IFNγ-specific gene networks, extensively connected with PI3K, MAPK, and NF-κB signaling pathways, were oppositely regulated by IL-18 and pan-HDACIs. Evidently, both TSA and CBHA caused a two- to fourfold induction of phosphatase and tensin homolog expression to counteract IL-18-induced proinflammatory signaling and cardiac hypertrophy. |
Databáze: | OpenAIRE |
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