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Transient Receptor Potential Ankyrin 1 Channels Modulate Inflammatory Response in Respiratory Cells from Patients with Cystic Fibrosis.
- Source :
-
American journal of respiratory cell and molecular biology [Am J Respir Cell Mol Biol] 2016 Nov; Vol. 55 (5), pp. 645-656. - Publication Year :
- 2016
-
Abstract
- Pseudomonas aeruginosa colonization, prominent inflammation with massive expression of the neutrophil chemokine IL-8, and luminal infiltrates of neutrophils are hallmarks of chronic lung disease in patients with cystic fibrosis (CF). The nociceptive transient receptor potential ankyrin (TRPA) 1 calcium channels have been recently found to be involved in nonneurogenic inflammation. Here, we investigate the role of TRPA1 in CF respiratory inflammatory models in vitro. Expression of TRPA1 was evaluated in CF lung tissue sections and cells by immunohistochemistry and immunofluorescence. Epithelial cell lines (A549, IB3-1, CuFi-1, CFBE41o <superscript>-</superscript> ) and primary cells from patients with CF were used to: (1) check TRPA1 function modulation, by Fura-2 calcium imaging; (2) down-modulate TRPA1 function and expression, by pharmacological inhibitors (HC-030031 and A-967079) and small interfering RNA silencing; and (3) assess the effect of TRPA1 down-modulation on expression and release of cytokines upon exposure to proinflammatory challenges, by quantitative RT-PCR and 27-protein Bioplex assay. TRPA1 channels are expressed in the CF pseudostratified columnar epithelium facing the bronchial lumina exposed to bacteria, where IL-8 is coexpressed. Inhibition of TRPA1 expression results in a relevant reduction of release of several cytokines, including IL-8 and the proinflammatory cytokines IL-1β and TNF-α, in CF primary bronchial epithelial cells exposed to P. aeruginosa and to the supernatant of mucopurulent material derived from the chronically infected airways of patients with CF. In conclusion, TRPA1 channels are involved in regulating the extent of airway inflammation driven by CF bronchial epithelial cells.
- Subjects :
- A549 Cells
Adult
Bronchi pathology
Cystic Fibrosis genetics
Cystic Fibrosis pathology
Cytokines genetics
Epithelial Cells metabolism
Epithelial Cells pathology
Female
Gene Silencing
Humans
Interleukin-8 genetics
Interleukin-8 metabolism
Male
Middle Aged
Models, Biological
Nerve Tissue Proteins antagonists & inhibitors
Pneumonia genetics
Pseudomonas aeruginosa physiology
RNA, Messenger genetics
RNA, Messenger metabolism
TRPA1 Cation Channel
Tissue Donors
Transcription, Genetic
Transient Receptor Potential Channels antagonists & inhibitors
Young Adult
Calcium Channels metabolism
Cystic Fibrosis complications
Lung pathology
Nerve Tissue Proteins metabolism
Pneumonia complications
Pneumonia pathology
Transient Receptor Potential Channels metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1535-4989
- Volume :
- 55
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of respiratory cell and molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 27281024
- Full Text :
- https://doi.org/10.1165/rcmb.2016-0089OC