The role of histone deacetylases in asthma and allergic diseases
Diverse cellular functions, including inflammatory gene expression, DNA repair, and cell proliferation, are regulated by histone acetylation. Transcriptional coactivators possess intrinsic histone acetyltransferase activity, and this activity drives inflammatory gene expression and the development o...
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| Veröffentlicht in: | Journal of allergy and clinical immunology 2008-03, Vol.121 (3), p.580-584 |
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| container_title | Journal of allergy and clinical immunology |
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| creator | Bhavsar, Pankaj, PhD Ahmad, Tehireem, BSc Adcock, Ian M., PhD |
| description | Diverse cellular functions, including inflammatory gene expression, DNA repair, and cell proliferation, are regulated by histone acetylation. Transcriptional coactivators possess intrinsic histone acetyltransferase activity, and this activity drives inflammatory gene expression and the development of tolerance in macrophages. Eleven histone deacetylases (HDACs) act to regulate the expression of distinct subsets of inflammatory/immune genes. Other proteins, particularly transcription factors, are also acetylated and are targets for deacetylation by HDACs and sirtuins, a group of protein deacetylases. HDAC inhibitors can further enhance inflammatory gene expression. However, the acetylation/deacetylation status of nonhistone proteins can also affect the overall expression pattern of inflammatory genes. HDAC2 expression and activity is reduced in lung macrophages, biopsy specimens, and blood cells from patients with severe asthma and smoking-induced asthma, as well as in patients with chronic obstructive pulmonary disease, perhaps accounting for the enhanced inflammation and reduced steroid responsiveness seen in these patients. Targeting specific enzymes involved in this process might lead to new therapeutic agents, particularly in situations in which current anti-inflammatory therapies are suboptimal. |
| doi_str_mv | 10.1016/j.jaci.2007.12.1156 |
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Transcriptional coactivators possess intrinsic histone acetyltransferase activity, and this activity drives inflammatory gene expression and the development of tolerance in macrophages. Eleven histone deacetylases (HDACs) act to regulate the expression of distinct subsets of inflammatory/immune genes. Other proteins, particularly transcription factors, are also acetylated and are targets for deacetylation by HDACs and sirtuins, a group of protein deacetylases. HDAC inhibitors can further enhance inflammatory gene expression. However, the acetylation/deacetylation status of nonhistone proteins can also affect the overall expression pattern of inflammatory genes. HDAC2 expression and activity is reduced in lung macrophages, biopsy specimens, and blood cells from patients with severe asthma and smoking-induced asthma, as well as in patients with chronic obstructive pulmonary disease, perhaps accounting for the enhanced inflammation and reduced steroid responsiveness seen in these patients. Targeting specific enzymes involved in this process might lead to new therapeutic agents, particularly in situations in which current anti-inflammatory therapies are suboptimal.</description><identifier>ISSN: 0091-6749</identifier><identifier>EISSN: 1097-6825</identifier><identifier>DOI: 10.1016/j.jaci.2007.12.1156</identifier><identifier>PMID: 18234319</identifier><identifier>CODEN: JACIBY</identifier><language>eng</language><publisher>New York, NY: Mosby, Inc</publisher><subject>Allergy and Immunology ; Animals ; Asthma - enzymology ; Asthma - genetics ; Biological and medical sciences ; Chromatin ; Cytokines ; DNA methylation ; Epigenesis, Genetic ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Gene Expression ; Gene Expression Regulation - genetics ; glucocorticoids ; Histone deacetylase ; Histone Deacetylases - metabolism ; Humans ; Hypersensitivity - enzymology ; Hypersensitivity - genetics ; immune tolerance ; Immune Tolerance - genetics ; inflammation ; Inflammation - genetics ; Kinases ; Medical sciences ; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. 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Transcriptional coactivators possess intrinsic histone acetyltransferase activity, and this activity drives inflammatory gene expression and the development of tolerance in macrophages. Eleven histone deacetylases (HDACs) act to regulate the expression of distinct subsets of inflammatory/immune genes. Other proteins, particularly transcription factors, are also acetylated and are targets for deacetylation by HDACs and sirtuins, a group of protein deacetylases. HDAC inhibitors can further enhance inflammatory gene expression. However, the acetylation/deacetylation status of nonhistone proteins can also affect the overall expression pattern of inflammatory genes. HDAC2 expression and activity is reduced in lung macrophages, biopsy specimens, and blood cells from patients with severe asthma and smoking-induced asthma, as well as in patients with chronic obstructive pulmonary disease, perhaps accounting for the enhanced inflammation and reduced steroid responsiveness seen in these patients. Targeting specific enzymes involved in this process might lead to new therapeutic agents, particularly in situations in which current anti-inflammatory therapies are suboptimal.</description><subject>Allergy and Immunology</subject><subject>Animals</subject><subject>Asthma - enzymology</subject><subject>Asthma - genetics</subject><subject>Biological and medical sciences</subject><subject>Chromatin</subject><subject>Cytokines</subject><subject>DNA methylation</subject><subject>Epigenesis, Genetic</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Gene Expression</subject><subject>Gene Expression Regulation - genetics</subject><subject>glucocorticoids</subject><subject>Histone deacetylase</subject><subject>Histone Deacetylases - metabolism</subject><subject>Humans</subject><subject>Hypersensitivity - enzymology</subject><subject>Hypersensitivity - genetics</subject><subject>immune tolerance</subject><subject>Immune Tolerance - genetics</subject><subject>inflammation</subject><subject>Inflammation - genetics</subject><subject>Kinases</subject><subject>Medical sciences</subject><subject>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. 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Psychology</topic><topic>Fundamental immunology</topic><topic>Gene Expression</topic><topic>Gene Expression Regulation - genetics</topic><topic>glucocorticoids</topic><topic>Histone deacetylase</topic><topic>Histone Deacetylases - metabolism</topic><topic>Humans</topic><topic>Hypersensitivity - enzymology</topic><topic>Hypersensitivity - genetics</topic><topic>immune tolerance</topic><topic>Immune Tolerance - genetics</topic><topic>inflammation</topic><topic>Inflammation - genetics</topic><topic>Kinases</topic><topic>Medical sciences</topic><topic>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. 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HDAC2 expression and activity is reduced in lung macrophages, biopsy specimens, and blood cells from patients with severe asthma and smoking-induced asthma, as well as in patients with chronic obstructive pulmonary disease, perhaps accounting for the enhanced inflammation and reduced steroid responsiveness seen in these patients. Targeting specific enzymes involved in this process might lead to new therapeutic agents, particularly in situations in which current anti-inflammatory therapies are suboptimal.</abstract><cop>New York, NY</cop><pub>Mosby, Inc</pub><pmid>18234319</pmid><doi>10.1016/j.jaci.2007.12.1156</doi><tpages>5</tpages></addata></record> |
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| subjects | Allergy and Immunology Animals Asthma - enzymology Asthma - genetics Biological and medical sciences Chromatin Cytokines DNA methylation Epigenesis, Genetic Fundamental and applied biological sciences. Psychology Fundamental immunology Gene Expression Gene Expression Regulation - genetics glucocorticoids Histone deacetylase Histone Deacetylases - metabolism Humans Hypersensitivity - enzymology Hypersensitivity - genetics immune tolerance Immune Tolerance - genetics inflammation Inflammation - genetics Kinases Medical sciences Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis |
| title | The role of histone deacetylases in asthma and allergic diseases |
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