Type

Other / n/a

Authors

Clifford C Taggart
Paul B McCray
Catherine M Greene
Noel G McElvaney
Christopher J Scott
Jennifer A Bartlett
Christine L Wohlford-Lenane
Irene K Oglesby
Danny F McAuley
Paul McNally
and 1 others

Subjects

Microbiology

Topics
enzyme linked immunosorbent assay interferon regulatory factor 1 biomarkers cell line medicine and health sciences pseudomonas aeruginosa bronchoalveolar lavage fluid respiratory mucosa humans micrornas infant cathepsins child preschool peptide hydrolases cystic fibrosis adolescent reverse transcriptase polymerase chain reaction preschool child down regulation pseudomonas infections blotting western blotting western

miR-31 dysregulation in cystic fibrosis airways contributes to increased pulmonary cathepsin S production. (2014)

Abstract RATIONALE: Cathepsin S (CTSS) activity is increased in bronchoalveolar lavage (BAL) fluid from patients with cystic fibrosis (CF). This activity contributes to lung inflammation via degradation of antimicrobial proteins, such as lactoferrin and members of the β-defensin family.OBJECTIVES: In this study, we investigated the hypothesis that airway epithelial cells are a source of CTSS, and mechanisms underlying CTSS expression in the CF lung.METHODS: Protease activity was determined using fluorogenic activity assays. Protein and mRNA expression were analyzed by ELISA, Western blotting, and reverse-transcriptase polymerase chain reaction.MEASUREMENTS AND MAIN RESULTS: In contrast to neutrophil elastase, CTSS activity was detectable in 100% of CF BAL fluid samples from patients without Pseudomonas aeruginosa infection. In this study, we identified epithelial cells as a source of pulmonary CTSS activity with the demonstration that CF airway epithelial cells express and secrete significantly more CTSS than non-CF control cells in the absence of proinflammatory stimulation. Furthermore, levels of the transcription factor IRF-1 correlated with increased levels of its target gene CTSS. We discovered that miR-31, which is decreased in the CF airways, regulates IRF-1 in CF epithelial cells. Treating CF bronchial epithelial cells with a miR-31 mimic decreased IRF-1 protein levels with concomitant knockdown of CTSS expression and secretion.CONCLUSIONS: The miR-31/IRF-1/CTSS pathway may play a functional role in the pathogenesis of CF lung disease and may open up new avenues for exploration in the search for an effective therapeutic target.
Collections Ireland -> Royal College of Surgeons in Ireland -> Medicine Articles
Ireland -> Royal College of Surgeons in Ireland -> Department of Medicine

Full list of authors on original publication

Clifford C Taggart, Paul B McCray, Catherine M Greene, Noel G McElvaney, Christopher J Scott, Jennifer A Bartlett, Christine L Wohlford-Lenane, Irene K Oglesby, Danny F McAuley, Paul McNally and 1 others

Experts in our system

1
Clifford C Taggart
Royal College of Surgeons in Ireland
Total Publications: 54
 
2
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150
 
3
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
4
Paul McNally
Royal College of Surgeons in Ireland
Total Publications: 26