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Bile Acids Repress Hypoxia-Inducible Factor 1 Signaling and Modulate the Airway Immune Response

Overview of attention for article published in Infection and Immunity, September 2014
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1 tweeter

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35 Mendeley
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Title
Bile Acids Repress Hypoxia-Inducible Factor 1 Signaling and Modulate the Airway Immune Response
Published in
Infection and Immunity, September 2014
DOI 10.1128/iai.00674-13
Pubmed ID
Authors

Claire Legendre, F. Jerry Reen, David F. Woods, Marlies J. Mooij, Claire Adams, Fergal O'Gara

Abstract

Gastroesophageal reflux (GER) frequently occurs in patients with respiratory disease and is particularly prevalent in patients with cystic fibrosis. 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 1α (HIF-1α) protein, an emerging master regulator in response to infection and inflammation. HIF-1α 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-1α 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-1α, 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.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 35 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 35 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 8 23%
Student > Ph. D. Student 5 14%
Student > Bachelor 5 14%
Researcher 3 9%
Student > Postgraduate 3 9%
Other 8 23%
Unknown 3 9%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 11 31%
Medicine and Dentistry 10 29%
Agricultural and Biological Sciences 6 17%
Immunology and Microbiology 3 9%
Social Sciences 1 3%
Other 1 3%
Unknown 3 9%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 November 2014.
All research outputs
#5,576,240
of 7,373,626 outputs
Outputs from Infection and Immunity
#1,868
of 2,517 outputs
Outputs of similar age
#130,431
of 200,433 outputs
Outputs of similar age from Infection and Immunity
#45
of 72 outputs
Altmetric has tracked 7,373,626 research outputs across all sources so far. This one is in the 13th percentile – i.e., 13% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,517 research outputs from this source. They receive a mean Attention Score of 3.8. This one is in the 16th percentile – i.e., 16% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 200,433 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 19th percentile – i.e., 19% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 72 others from the same source and published within six weeks on either side of this one. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.