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To characterize glucocorticoid\u2010induced modulation of gene expression in the human airways, we performed a randomized placebo\u2010controlled crossover study in healthy male volunteers. Six hours after placebo or budesonide inhalation, whole blood, bronchial brushings, and endobronchial biopsies were collected. Microarray analysis of biopsy <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>, using stringent (\u22652\u2010fold, 5% false discovery rate) or less stringent (\u22651.25\u2010fold, <jats:italic>P\u00a0<\/jats:italic>\u2264<jats:italic>\u00a0<\/jats:italic>0.05) criteria, identified 46 and 588 budesonide\u2010induced genes, respectively. Approximately two third of these genes are transcriptional regulators (<jats:styled-content style=\"fixed-case\">KLF<\/jats:styled-content>9, <jats:styled-content style=\"fixed-case\">PER<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>22D3, <jats:styled-content style=\"fixed-case\">ZBTB<\/jats:styled-content>16), receptors (<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>163, <jats:styled-content style=\"fixed-case\">CNR<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4, <jats:styled-content style=\"fixed-case\">LIFR<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> TLR<\/jats:styled-content>2), or signaling genes (<jats:styled-content style=\"fixed-case\">DUSP<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">NFKBIA<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> RGS<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">RGS<\/jats:styled-content>2, <jats:styled-content style=\"fixed-case\">ZFP<\/jats:styled-content>36). Listed genes were <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content> verified. Expression of anti\u2010inflammatory and other potentially beneficial genes is therefore confirmed and consistent with gene ontology (<jats:styled-content style=\"fixed-case\">GO<\/jats:styled-content>) terms for negative regulation of transcription and gene expression. However, <jats:styled-content style=\"fixed-case\">GO<\/jats:styled-content> terms for transcription, signaling, metabolism, proliferation, inflammatory responses, and cell movement were also associated with the budesonide\u2010induced genes. The most enriched functional cluster indicates positive regulation of proliferation, locomotion, movement, and migration. Moreover, comparison with the budesonide\u2010induced expression profile in primary human airway epithelial cells shows considerable cell type specificity. In conclusion, increased expression of multiple genes, including the transcriptional repressor, <jats:styled-content style=\"fixed-case\">ZBTB<\/jats:styled-content>16, that reduce inflammatory signaling and gene expression, occurs in the airways and blood and may contribute to the therapeutic efficacy of <jats:styled-content style=\"fixed-case\">ICS<\/jats:styled-content>. This provides a previously lacking insight into the in\u00a0vivo effects of <jats:styled-content style=\"fixed-case\">ICS<\/jats:styled-content> and should promote strategies to improve glucocorticoid efficacy in inflammatory diseases.<\/jats:p>","DOI":"10.1002\/prp2.243","type":"journal-article","created":{"date-parts":[[2016,7,12]],"date-time":"2016-07-12T06:14:32Z","timestamp":1468304072000},"source":"Crossref","is-referenced-by-count":55,"title":["An inhaled dose of budesonide induces genes involved in transcription and signaling in the human airways: enhancement of anti\u2010 and proinflammatory effector genes"],"prefix":"10.1002","volume":"4","author":[{"given":"Richard","family":"Leigh","sequence":"first","affiliation":[{"name":"Airways Inflammation Research Group Snyder Institute for Chronic Diseases University of Calgary Calgary Alberta T2N 4Z6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud 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