Abstract
The hypoxic environment of cystic fibrosis airways allows the persistence of facultative anaerobic bacteria, which can produce short-chain fatty acids (SCFAs) through fermentation. However, the relevance of SCFAs in cystic fibrosis lung disease is unknown. We show that SCFAs are present in sputum samples from cystic fibrosis patients in millimolar concentrations (mean±sem 1.99±0.36 mM).
SCFAs positively correlated with sputum neutrophil count and higher SCFAs were predictive for impaired nitric oxide production. We studied the effects of the SCFAs acetate, propionate and butyrate on airway inflammatory responses using epithelial cell lines and primary cell cultures. SCFAs in concentrations present in cystic fibrosis airways (0.5–2.5 mM) affected the release of granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor and interleukin (IL)-6. SCFAs also resulted in higher IL-8 release from stimulated cystic fibrosis transmembrane conductance regulator (CFTR) F508del-mutant compared to wild-type CFTR-corrected bronchial epithelial cells. At 25 mM propionate reduced IL-8 release in control but not primary cystic fibrosis epithelial cells. Low (0.5–2.5 mM) SCFA concentrations increased, while high (25–50 mM) concentrations decreased inducible nitric oxide synthase expression. In addition, SCFAs affected the growth of Pseudomonas aeruginosa in a concentration- and pH-dependent manner.
Thus, our data suggest that SCFAs contribute to cystic fibrosis-specific alterations of responses to airway infection and inflammation.
Abstract
Short-chain fatty acids contribute to CF-specific alterations of responses to airway infection and inflammation http://ow.ly/L7ZI9
Footnotes
This article has supplementary material available from erj.ersjournals.com
Support statement: This research was supported by the Lynne and Arnold Irwin Foundation and the Cystic Fibrosis Centre at the Hospital for Sick Children (Toronto, ON, Canada; 2014 CF Centre Catalyst Research Grant). N. Palaniyar was supported by Cystic Fibrosis Canada (grant 2619). P. Ghorbani was supported in part by an Ontario Graduate Scholarship. Funding information for this article has been deposited with FundRef.
Conflict of interest: Disclosures can be found alongside the online version of this article at erj.ersjournals.com
- Received August 5, 2014.
- Accepted March 30, 2015.
- Copyright ©ERS 2015