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Histone deacetylase and acetyltransferase inhibitors decrease organic dust-mediated activation of proinflammatory gene expression.

Authors
LeVan-TD; Weiler-Z; Romberger-DJ
Source
Am J Respir Crit Care Med 2010 May; 181(Meeting Abstracts):A2010
NIOSHTIC No.
20037110
Abstract
RATIONALE: Post-translational modification of histone proteins are major mechanisms that modify chromatin structure and regulate gene expression in eukaryotes. Activation of histone acetyltransferase (HAT) or inhibition of histone deacetylases (HDAC) is generally believed to allow chromatin to assume a more open state, permitting transcriptional activity. METHODS: Organic dust was obtained from settled surface dust from swine confinement facilities and extracted in Hanks' balanced salt solution. Bronchial epithelial cells, BEAS-2B cell line, were pretreated for 30-120 min with trichostatin A (1-10 ug/ml) and anacardic acid (0.1 to 1 uM), then stimulated with organic dust for 4 hours. Cell-free supernatants were harvested and assayed for IL-6 and IL-8 by ELISA. RESULTS: We report here the surprising observation that treatment of a human bronchial epithelial cell line, BEAS-2B cells, with the inhibitor histone deacetylase, trichostatin A, or the histone acetyltransferase inhibitor, anacardic acid, strongly inhibited induction of both IL-6 and IL-8 protein upon stimulation with organic dust. CONCLUSION: These data suggest that chromatin remodeling regulates organic dust-induced IL-6 and IL-8 protein production. The mechanism (s) of this regulation will be an area of future investigation.
Keywords
Agricultural-industry; Agricultural-processes; Agricultural-workers; Agriculture; Airborne-particles; Biological-effects; Biological-monitoring; Breathing; Bronchial-asthma; Cell-transformation; Cellular-reactions; Dust-exposure; Dust-inhalation; Dust-measurement; Dust-particles; Exposure-assessment; Exposure-levels; Exposure-methods; Genes; Genetic-factors; Inhalants; Inhalation-studies; Lung; Lung-cells; Lung-disease; Lung-disorders; Lung-irritants; Occupational-diseases; Occupational-exposure; Occupational-hazards; Occupational-health; Occupational-respiratory-disease; Organic-dusts; Particulate-dust; Pulmonary-disorders; Pulmonary-system; Pulmonary-system-disorders; Respirable-dust; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-rate; Respiratory-system-disorders; Risk-analysis; Risk-factors; Statistical-analysis; Treatment; Work-areas; Work-environment; Work-operations; Work-performance; Workplace-studies; Work-practices
CODEN
AJCMED
Publication Date
20100501
Document Type
Abstract
Funding Type
Grant
Fiscal Year
2010
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-008539
ISSN
1073-449X
Priority Area
Agriculture, Forestry and Fishing
Source Name
American Journal of Respiratory and Critical Care Medicine
State
NE
Performing Organization
University of Nebraska
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