Hypoxia-inducible factor and bacterial infections in chronic obstructive pulmonary disease

Shukla, SD; Walters, EH; Simpson, JL; Keely, S; Wark, PAB; O'Toole, RF; Hansbro, PM

Hypoxia-inducible factor and bacterial infections in chronic obstructive pulmonary disease

Shukla, SD

Walters, EH Simpson, JL

Keely, S Wark, PAB

O'Toole, RF

Hansbro, PM

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Publication Type:: Journal Article
Citation:: Respirology, 2020, 25 (1), pp. 53 - 63
Issue Date:: 2020-01-01

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Field	Value	Language
dc.contributor.author	Shukla, SD https://orcid.org/0000-0002-5796-0171	en_US
dc.contributor.author	Walters, EH	en_US
dc.contributor.author	Simpson, JL https://orcid.org/0000-0002-3626-680X	en_US
dc.contributor.author	Keely, S	en_US
dc.contributor.author	Wark, PAB https://orcid.org/0000-0001-5676-6126	en_US
dc.contributor.author	O'Toole, RF https://orcid.org/0000-0002-4579-4479	en_US
dc.contributor.author	Hansbro, PM https://orcid.org/0000-0002-4741-3035	en_US
dc.date.available	2019-10-08	en_US
dc.date.issued	2020-01-01	en_US
dc.identifier.citation	Respirology, 2020, 25 (1), pp. 53 - 63	en_US
dc.identifier.issn	1323-7799	en_US
dc.identifier.uri	http://hdl.handle.net/10453/136762
dc.description.abstract	© 2019 Asian Pacific Society of Respirology COPD is a seriously disabling respiratory condition that inexorably progresses to disability and mortality. It affects approximately 10% of the population globally with a greater prevalence at advanced ages. Airway bacterial infections complicate the disease course in most COPD patients, leading to increased symptoms, more rapid decline in lung function, acute exacerbations and reduced quality of life. With increasing bacterial resistance to antibiotics and adverse effects of conventional treatments, new effective non-antibiotic antimicrobial therapies are urgently needed to manage COPD. Hypoxia-inducible factor (HIF)-1α is an important transcriptional regulator of cellular responses to hypoxia, oxidants and inflammation, and is overexpressed in the lungs of COPD patients. Recent evidence shows that increased HIF-1α expression can upregulate the platelet-activating factor receptor (PAFR) on the airway epithelial surface that is increased in smokers and particularly COPD patients. The receptor is utilized by PAFR-dependent bacteria (Streptococcus pneumoniae, Haemophilus influenzae and Pseudomonas aeruginosa) to induce infection in both the respiratory and gastrointestinal (GI) tracts. However, the importance and mechanism of HIF-1α in augmenting PAFR-dependent bacterial infections in COPD are poorly understood. Here, we review the evidence for the roles of local tissue hypoxia-induced inflammation, HIF-1α and PAFR in facilitating bacterial infections in COPD. Blocking PAFR may provide a novel antimicrobial approach to manage bacterial infections in COPD.	en_US
dc.relation	http://purl.org/au-research/grants/nhmrc/APP1099095
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT1079187
dc.relation	http://purl.org/au-research/grants/nhmrc/1175134
dc.relation.ispartof	Respirology	en_US
dc.relation.isbasedon	10.1111/resp.13722	en_US
dc.subject.classification	Respiratory System	en_US
dc.title	Hypoxia-inducible factor and bacterial infections in chronic obstructive pulmonary disease	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	25	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	25	en_US

Abstract:

© 2019 Asian Pacific Society of Respirology COPD is a seriously disabling respiratory condition that inexorably progresses to disability and mortality. It affects approximately 10% of the population globally with a greater prevalence at advanced ages. Airway bacterial infections complicate the disease course in most COPD patients, leading to increased symptoms, more rapid decline in lung function, acute exacerbations and reduced quality of life. With increasing bacterial resistance to antibiotics and adverse effects of conventional treatments, new effective non-antibiotic antimicrobial therapies are urgently needed to manage COPD. Hypoxia-inducible factor (HIF)-1α is an important transcriptional regulator of cellular responses to hypoxia, oxidants and inflammation, and is overexpressed in the lungs of COPD patients. Recent evidence shows that increased HIF-1α expression can upregulate the platelet-activating factor receptor (PAFR) on the airway epithelial surface that is increased in smokers and particularly COPD patients. The receptor is utilized by PAFR-dependent bacteria (Streptococcus pneumoniae, Haemophilus influenzae and Pseudomonas aeruginosa) to induce infection in both the respiratory and gastrointestinal (GI) tracts. However, the importance and mechanism of HIF-1α in augmenting PAFR-dependent bacterial infections in COPD are poorly understood. Here, we review the evidence for the roles of local tissue hypoxia-induced inflammation, HIF-1α and PAFR in facilitating bacterial infections in COPD. Blocking PAFR may provide a novel antimicrobial approach to manage bacterial infections in COPD.

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http://hdl.handle.net/10453/136762