- Title
- Hypoxia-inducible factor and bacterial infections in chronic obstructive pulmonary disease
- Creator
- Shukla, Shakti D.; Walters, E. Haydn; Simpson, Jodie L.; Keely, Simon; Wark, Peter A. B.; O'Toole, Ronan F.; Hansbro, Philip M.
- Relation
- NHMRC.1079187 http://purl.org/au-research/grants/nhmrc/1079187 & NHMRC 1175134
- Relation
- Respirology Vol. 25, Issue 1, p. 53-63
- Publisher Link
- http://dx.doi.org/10.1111/resp.13722
- Publisher
- Wiley-Blackwell
- Resource Type
- journal article
- Date
- 2020
- Description
- 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 tran-scriptional regulator of cellular responses to hypoxia, oxidants and inflammation, and is over expressed 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 gastroin-testinal (GI) tracts. However, the importance and mechanism of HIF-1αin 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.
- Subject
- airway infections; bacterial adhesion; chronic obstructive pulmonary disease; hypoxia-inducible factor; platelet-activating factor receptor; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1436397
- Identifier
- uon:40012
- Identifier
- ISSN:1323-7799
- Language
- eng
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