Type

Journal Article

Authors

Noel G McElvaney
Emer P Reeves
Philip Murphy
Patrick M Logan
Kevin Kavanagh
Cedric Gunaratnam
Catherine M Greene
Katie Dunne
Kathleen Bennett
Ahmed Eshwika
and 6 others

Subjects

Microbiology

Topics
pharmacology epithelium itraconazole high resolution vitamin d blotting western microbiology epithelial cells complications th2 cells interleukin 5 aspergillosis allergic bronchopulmonary vitamin d supplementation bronchi cells cultured adult metabolism bronchoalveolar lavage fluid humans immunosuppressive agents cystic fibrosis reverse transcriptase polymerase chain reaction female therapeutic use down regulation aspergillus fumigatus drug therapy interleukin 13 pulmonary aspergillosis male gliotoxin receptors calcitriol trachea young adult antifungal agents

The effect of Aspergillus fumigatus infection on vitamin D receptor expression in cystic fibrosis. (2012)

Abstract Aspergillus fumigatus (A. fumigatus) in cystic fibrosis (CF) is increasingly recognized. Although allergic bronchopulmonary aspergillosis (ABPA) leads to deterioration of pulmonary function, the effect of A. fumigatus colonization in the absence of ABPA remains unclear. To address this, we examined individuals with CF with A. fumigatus who were ABPA negative to identify the effects of itraconazole therapy on Aspergillus-induced lung inflammation. The effect of A. fumigatus on nuclear vitamin D receptor (VDR) expression was investigated using qRT-PCR and Western blotting. IL-5 and IL-13 levels were quantified by ELISA. The effect of itraconazole was assessed by a combination of high-resolution computed tomography, lung function test, and microbiological analysis. We demonstrate that A. fumigatus down-regulates VDR in macrophages and airway epithelial cells and that the fungal metabolite gliotoxin (Gt) is the main causative agent. Gt overcame the positive effect of 1,25-OH vitamin D(3) on VDR expression in vitro, resulting in increased IL-5 and IL-13 production. In vivo, A. fumigatus positivity was associated with increased Gt in CF bronchoalveolar lavage fluid and increased bronchoalveolar lavage fluid levels of IL-5 and IL-13. After airway eradication of A. fumigatus with itraconazole, we observed decreased Gt, IL-5 and IL-13, improved respiratory symptoms, and diminished high-resolution computed tomography mosaic pattern consistent with sustained pulmonary function. This study provides a rationale for the therapeutic effect of itraconazole and implied that the therapeutic potential of vitamin D supplementation in preventing ABPA is only feasible with concurrent elimination of A. fumigatus to permit VDR expression and its positive functional consequences.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed
Ireland -> Maynooth University -> Academic Unit = Faculty of Science and Engineering: Biology
Ireland -> Maynooth University -> Type = Article
Ireland -> Maynooth University -> Academic Unit = Faculty of Science and Engineering
Ireland -> Maynooth University -> Status = Published
Ireland -> Maynooth University -> Open Access DRIVERset

Full list of authors on original publication

Noel G McElvaney, Emer P Reeves, Philip Murphy, Patrick M Logan, Kevin Kavanagh, Cedric Gunaratnam, Catherine M Greene, Katie Dunne, Kathleen Bennett, Ahmed Eshwika and 6 others

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Emer P Reeves
Royal College of Surgeons in Ireland
Total Publications: 63
 
3
Philip Murphy
TU Dublin (Tallaght Campus)
Total Publications: 30
 
4
Kevin Kavanagh
Maynooth University
Total Publications: 183
 
5
Cedric Gunaratnam
Royal College of Surgeons in Ireland
Total Publications: 18
 
6
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150
 
7
Katie Dunne
Trinity College Dublin
Total Publications: 10
 
8
Kathleen Bennett
Royal College of Surgeons in Ireland
Total Publications: 137
 
9
Ahmed Eshwika
Maynooth University
Total Publications: 6