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2612070 
Journal Article 
Abstract 
Histone deacetylase and acetyltransferase inhibitors decrease organic dust-mediated activation of proinflammatory gene expression 
Levan, TD; Weiler, Z; Romberger, DJ 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A2010 
English 
WOS:000208771001217 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
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. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010