Published ahead of print on December 23, 2004, doi:10.1164/rccm.200404-532OC Am. J. Respir. Crit. Care Med., Volume 171, Number 6, March 2005, 579-586 A more recent version of this article appeared on March 15, 2005
Submitted on April 23, 2004 Effects of Allergen Challenge on Airway Epithelial Cell Gene ExpressionCraig M Lilly1*,1 The Combined Progran in Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, 2 The Combined Progran in Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Cardiopulmonary Division and Department of Medicine, Keio University School of Medicine, Tokyo, Japan, 3 The Combined Progran in Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Thermal and Mountain Division, US Army Research Institute of Environmental Medicine, Natick, MA, USA * To whom correspondence should be addressed. E-mail: clilly{at}partners.org.
Allergen exposure induces the airway epithelium to produce chemoattractants, pro-allergic interleukins, matrix-modifying proteins, and proteins that influence the growth and activation state of airway structural cells. These proteins in turn contribute to the influx of inflammatory cells and changes in structure that characterize the asthmatic airway. To use the response of the airway epithelium to allergen to identify genes not previously associated with allergic responses, we compared gene expression in cytokeratin-positive cells before and after segmental allergen challenge. After challenge with concentrations of allergen in the clinically relevant range, 755 (6%) of the detectable sequences had geometric mean fold-changes in expression with 95% confidence intervals that excluded unity. Using a prospectively defined conservative filtering algorithm, we identified 141 sequences as upregulated and 8 as downregulated, with confirmation by conventional PCR in all 10 sequences studied. Using this approach we identified asthma-associated sequences including interleukin (IL) -3,-4, and -5 receptor subunits, the p65 component of NF-kappaB, and lipocortin. The genomic response of the human airway to concentrations of allergen in the clinically relevant range involves a greater number of genes than previously recognized, including many not previously associated with asthma that are differentially expressed after airway allergen exposure. Key words: genomics, asthma, segmental allergen challenge, lung disease allergen,
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