Type

Journal Article

Authors

Noel G McElvaney
Catherine M Greene
Rosaleen Devery
Marianne S Muhlebach
Michael M Tunney
Matthew Wolfgang
Joe Hatch
Paul McNally
Dubhfeasa Slattery
Fiona Healy
and 6 others

Subjects

Biochemistry

Topics
protein expression fatty acids cystic fibrosis endoplasmic reticulum stress bacteria anaerobic laser scanning cytometry acetic acid epithelial cells

Short-chain Fatty Acids Cause an IL-8 Response in Cystic Fibrosis Airways via Increased GPR41. (2015)

Abstract Anaerobic bacteria are present in large numbers in the airways of people with cystic fibrosis (PWCF). In the gut, anaerobes produce short-chain fatty acids (SCFAs) that modulate immune/inflammatory processes. To investigate the capacity of anaerobes to contribute to CF airway pathogenesis via SCFAs. Samples from 109 PWCF were processed using anaerobic microbiological culture with bacteria present identified by 16S RNA sequencing. SCFAs levels in anaerobe supernatants and bronchoalveolar lavage (BAL) were determined by gas chromatography. The mRNA and/or protein expression of SCFAs receptors, GPR41 and GPR43, in CF and non-CF bronchial brushings, and 16HBE14o- and CFBE41o- cells were evaluated using RT-PCR, western blot, laser scanning cytometry and confocal microscopy. SCFAs-induced IL-8 secretion was monitored by ELISA. Fifty seven of 109 (52.3%) PWCF were anaerobe-positive. Prevalence increased with age, from 33.3% to 57.7% in PWCF under (n=24) and over 6 years (n=85). All evaluated anaerobes produced millimolar concentrations of SCFAs, including acetic, propionic and butyric acid. SCFAs levels were higher in BAL samples from adults than children. GPR41 levels were elevated in; CFBE41o- versus 16HBE14o- cells; CF versus non-CF bronchial brushings; 16HBE14o- cells after treatment with CFTR inhibitor CFTR(inh)-172, CF BAL, or inducers of endoplasmic reticulum stress. SCFAs induced a dose-dependent and pertussis toxin-sensitive IL-8 response in bronchial epithelial cells with a higher production of IL-8 in CFBE41o- than 16HBE14o- cells. This study illustrates that SCFAs contribute to excessive production of IL-8 in CF airways colonized with anaerobes via upregulated GPR41.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

Noel G McElvaney, Catherine M Greene, Rosaleen Devery, Marianne S Muhlebach, Michael M Tunney, Matthew Wolfgang, Joe Hatch, Paul McNally, Dubhfeasa Slattery, Fiona Healy and 6 others

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150
 
3
R Devery
Dublin City University
Total Publications: 36
 
4
Paul McNally
Royal College of Surgeons in Ireland
Total Publications: 26