Histone acetylation regulates epithelial IL-8 release mediated by oxidative stress from environmental particles.
Increases in the levels of environmental particulate matter with a diameter of <10 microm diameter (PM(10)) in the air are associated with a variety of adverse health effects, particularly chronic lung and cardiovascular diseases. The expression of many inflammatory genes involves the remodeling of the chromatin structure provided by histone proteins. Histone acetylation causes the unwinding of chromatin structure, therefore allowing transcription factor access to promoter sites. Acetylation is reversible and is regulated by histone acetyltransferases (HATs), which promote acetylation, and deacetylases, which promote deacetylation. PM(10) and H(2)O(2) increased IL-8 protein release from A549 cells after 24-h treatment, and this was enhanced by histone deacetylase inhibition by trichostatin A (cotreatment). PM(10) and H(2)O(2) treatment also increased HAT activity as well as the level of acetylated histone 4 (H4). PM(10) enhanced H4 acetylation that was mediated by oxidative stress as shown by thiol antioxidant inhibition. Acetylation of H4 mediated by PM(10) was associated with the promoter region of the IL-8 gene. These data suggest that remodeling of chromatin by histone acetylation plays a role in PM(10)-mediated responses in the lungs.
Gilmour
Peter S
PS
Edinburgh Lung and the Environment Group Initiative/Colt Laboratory, The University of Edinburgh, Department of Medicine and Radiological Sciences, Medical School, Edinburgh EH8 9AG, United Kingdom.
Rahman
Irfan
I
Donaldson
Kenneth
K
MacNee
William
W
D000107:Acetylation / Q000187:drug effects; D000393:Air Pollutants / Q000494:pharmacology*; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D056464:Histone Deacetylase 2; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010316:Particle Size; D011401:Promoter Regions, Genetic; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D000393:Air Pollutants; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D016209:Interleukin-8; D016328:NF-kappa B; D016877:Oxidants; D012333:RNA, Messenger; D012097:Repressor Proteins; D006861:Hydrogen Peroxide; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases