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GER is a condition in which the duodenogastric contents of the stomach leak into the esophagus, in many cases resulting in aspiration into the respiratory tract. As such, the presence of GER-derived bile acids (BAs) has been confirmed in the bronchoalveolar lavage fluid and sputum of affected patients. We have recently shown that bile causes cystic fibrosis-associated bacterial pathogens to adopt a chronic lifestyle and may constitute a major host trigger underlying respiratory infection. The current study shows that BAs elicit a specific response in humans in which they repress hypoxia-inducible factor 1\u03b1 (HIF-1\u03b1) protein, an emerging master regulator in response to infection and inflammation. HIF-1\u03b1 repression was shown to occur through the 26S proteasome machinery via the prolyl hydroxylase domain (PHD) pathway. Further analysis of the downstream inflammatory response showed that HIF-1\u03b1 repression by BAs can significantly modulate the immune response of airway epithelial cells, correlating with a decrease in interleukin-8 (IL-8) production, while IL-6 production was strongly increased. Importantly, the effects of BAs on cytokine production can also be more dominant than the bacterium-mediated effects. However, the effect of BAs on cytokine levels cannot be fully explained by their ability to repress HIF-1\u03b1, which is not surprising, given the complexity of the immune regulatory network. The suppression of HIF-1 signaling by bile acids may have a significant influence on the progression and outcome of respiratory disease, and the molecular mechanism underpinning this response warrants further investigation.<\/jats:p>","DOI":"10.1128\/iai.00674-13","type":"journal-article","created":{"date-parts":[[2014,6,10]],"date-time":"2014-06-10T03:24:29Z","timestamp":1402370669000},"page":"3531-3541","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Bile Acids Repress Hypoxia-Inducible Factor 1 Signaling and Modulate the Airway Immune Response"],"prefix":"10.1128","volume":"82","author":[{"given":"Claire","family":"Legendre","sequence":"first","affiliation":[{"name":"BIOMERIT Research Centre, School of Microbiology, University College Cork, Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. 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