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Histone Acetylase and Deacetylase Activity in Alveolar Macrophages and Blood Mononocytes in Asthma
by
Barnes, Peter J
, Chung, K. Fan
, Cosio, Borja G
, Jazrawi, Elen
, Mann, Buphinder
, Adcock, Ian M
, Ito, Kazuhiro
in
Acetyltransferases - metabolism
/ Adult
/ Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
/ Asthma - classification
/ Asthma - enzymology
/ Biological and medical sciences
/ Bronchoalveolar Lavage Fluid - immunology
/ Cytokines - drug effects
/ Cytokines - metabolism
/ Female
/ Glucocorticoids - therapeutic use
/ Histone Acetyltransferases
/ Histone Deacetylases - metabolism
/ Humans
/ Intensive care medicine
/ Macrophages, Alveolar - enzymology
/ Male
/ Medical sciences
/ Middle Aged
/ Monocytes - enzymology
/ Prednisolone - therapeutic use
2004
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Histone Acetylase and Deacetylase Activity in Alveolar Macrophages and Blood Mononocytes in Asthma
by
Barnes, Peter J
, Chung, K. Fan
, Cosio, Borja G
, Jazrawi, Elen
, Mann, Buphinder
, Adcock, Ian M
, Ito, Kazuhiro
in
Acetyltransferases - metabolism
/ Adult
/ Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
/ Asthma - classification
/ Asthma - enzymology
/ Biological and medical sciences
/ Bronchoalveolar Lavage Fluid - immunology
/ Cytokines - drug effects
/ Cytokines - metabolism
/ Female
/ Glucocorticoids - therapeutic use
/ Histone Acetyltransferases
/ Histone Deacetylases - metabolism
/ Humans
/ Intensive care medicine
/ Macrophages, Alveolar - enzymology
/ Male
/ Medical sciences
/ Middle Aged
/ Monocytes - enzymology
/ Prednisolone - therapeutic use
2004
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Histone Acetylase and Deacetylase Activity in Alveolar Macrophages and Blood Mononocytes in Asthma
by
Barnes, Peter J
, Chung, K. Fan
, Cosio, Borja G
, Jazrawi, Elen
, Mann, Buphinder
, Adcock, Ian M
, Ito, Kazuhiro
in
Acetyltransferases - metabolism
/ Adult
/ Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
/ Asthma - classification
/ Asthma - enzymology
/ Biological and medical sciences
/ Bronchoalveolar Lavage Fluid - immunology
/ Cytokines - drug effects
/ Cytokines - metabolism
/ Female
/ Glucocorticoids - therapeutic use
/ Histone Acetyltransferases
/ Histone Deacetylases - metabolism
/ Humans
/ Intensive care medicine
/ Macrophages, Alveolar - enzymology
/ Male
/ Medical sciences
/ Middle Aged
/ Monocytes - enzymology
/ Prednisolone - therapeutic use
2004
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Histone Acetylase and Deacetylase Activity in Alveolar Macrophages and Blood Mononocytes in Asthma
Journal Article
Histone Acetylase and Deacetylase Activity in Alveolar Macrophages and Blood Mononocytes in Asthma
2004
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Overview
Histone acetylation status is a key factor in the regulation of inflammatory gene transcription. We investigated the activity of histone acetylases (HAT) and deacetylases (HDAC), and the effect of glucocorticoids in alveolar macrophages (AM) and peripheral blood mononuclear cells (PBMC) from subjects with asthma. Bronchoalveolar lavage was performed in 10 patients with intermittent asthma, 8 with persistent asthma, and 10 healthy control subjects. PBMCs and granulocytes were isolated from six patients with mild and severe asthma, before and after a 7-day course of prednisolone (30 mg/day). AMs were isolated for HDAC assay or incubated with dexamethasone (1 microM). HAT activity was increased (1.43 +/- 0.1 vs. 1.01 +/- 0.1 standard units/10 microg, p < 0.05), and HDAC activity was reduced (3031 +/- 243 vs. 5004 +/- 164 arbitrary fluorescence units/10 microg, p < 0.001) in AMs of subjects with asthma compared with control subjects. Dexamethasone suppressed LPS-induced granulocyte macrophage-colony stimulating factor, tumor necrosis factor-alpha, and interleukin-8 release by 83 +/- 1%, 51 +/- 7% and 20 +/- 9% (p < 0.001), respectively. Similar effects were seen on nuclear factor-kappaB inhibition, and interleukin-8 release was further reduced by the HDAC enhancer, theophylline (37 +/- 6%). Prednisolone increased HDAC activity in PBMCs from subjects with mild asthma. The increased inflammatory response in asthma may be due to reduced HDAC and enhanced HAT activity. Glucocorticoids and theophylline may downregulate the inflammatory response by modulating HAT and HDAC activity, and nuclear factor-kappaB activation.
Publisher
Am Thoracic Soc,American Lung Association,American Thoracic Society
Subject
Acetyltransferases - metabolism
/ Adult
/ Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
/ Biological and medical sciences
/ Bronchoalveolar Lavage Fluid - immunology
/ Female
/ Glucocorticoids - therapeutic use
/ Histone Deacetylases - metabolism
/ Humans
/ Macrophages, Alveolar - enzymology
/ Male
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