Type

Journal Article

Authors

Noel G McElvaney
Mitsuomi Hirashima
Shane J O'Neill
Paul McNally
Tomohiro Arikawa
Toshiro Niki
Emer P Reeves
Isabel Vega-Carrascal

Subjects

Biochemistry

Topics
enzymology bronchi lgals9 protein human respiratory mucosa adult cftr protein human metabolism bronchoalveolar lavage fluid humans recombinant proteins cystic fibrosis transmembrane conductance regulator cystic fibrosis immunology female antagonists inhibitors signal transduction pathology biosynthesis up regulation neutrophils male ligands young adult aged havcr2 protein human membrane proteins middle aged cell line transformed physiology pharmacology galectins child

Dysregulation of TIM-3-galectin-9 pathway in the cystic fibrosis airways. (2011)

Abstract The T-cell Ig and mucin domain-containing molecules (TIMs) have emerged as promising therapeutic targets to correct abnormal immune function in several autoimmune and chronic inflammatory conditions. It has been reported that proinflammatory cytokine dysregulation and neutrophil-dominated inflammation are the main causes of morbidity in cystic fibrosis (CF). However, the role of TIM receptors in CF has not been investigated. In this study, we demonstrated that TIM-3 is constitutively overexpressed in the human CF airway, suggesting a link between CF transmembrane conductance regulator (CFTR) function and TIM-3 expression. Blockade of CFTR function with the CFTR inhibitor-172 induced an upregulation of TIM-3 and its ligand galectin-9 in normal bronchial epithelial cells. We also established that TIM-3 serves as a functional receptor in bronchial epithelial cells, and physiologically relevant concentrations of galectin-9 induced TIM-3 phosphorylation, resulting in increased IL-8 production. In addition, we have demonstrated that both TIM-3 and galectin-9 undergo rapid proteolytic degradation in the CF lung, primarily because of neutrophil elastase and proteinase-3 activity. Our results suggest a novel intrinsic defect that may contribute to the neutrophil-dominated immune response in the CF airways.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Noel G McElvaney, Mitsuomi Hirashima, Shane J O'Neill, Paul McNally, Tomohiro Arikawa, Toshiro Niki, Emer P Reeves, Isabel Vega-Carrascal

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Shane J O'Neill
Royal College of Surgeons in Ireland
Total Publications: 84
 
3
Paul McNally
Royal College of Surgeons in Ireland
Total Publications: 26
 
4
Emer P Reeves
Royal College of Surgeons in Ireland
Total Publications: 63