TRPV2 modulates mechanically Induced ATP Release from Human bronchial epithelial cells

Autor: Orla M. Dunne, S. Lorraine Martin, Gerard P. Sergeant, Daniel F. McAuley, Cecilia M. O’Kane, Brian Button, Lorcan P. McGarvey, Fionnuala T. Lundy
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Respiratory Research, Vol 25, Iss 1, Pp 1-10 (2024)
Druh dokumentu: article
ISSN: 1465-993X
DOI: 10.1186/s12931-024-02807-0
Popis: Abstract Repetitive bouts of coughing expose the large airways to significant cycles of shear stress. This leads to the release of alarmins and the tussive agent adenosine triphosphate (ATP) which may be modulated by the activity of ion channels present in the human airway. This study aimed to investigate the role of the transient receptor potential subfamily vanilloid member 2 (TRPV2) channel in mechanically induced ATP release from primary bronchial epithelial cells (PBECs). PBECs were obtained from individuals undergoing bronchoscopy. They were cultured in vitro and exposed to mechanical stress in the form of compressive and fluid shear stress (CFSS) or fluid shear stress (FSS) alone at various intensities. ATP release was measured using a luciferin–luciferase assay. Functional TRPV2 protein expression in human PBECs was investigated by confocal calcium imaging. The role of TRPV2 inhibition on FSS-induced ATP release was investigated using the TRPV2 inhibitor tranilast or siRNA knockdown of TRPV2. TRPV2 protein expression in human lung tissue was also determined by immunohistochemistry. ATP release was significantly increased in PBECs subjected to CFSS compared with control (unstimulated) PBECs (N = 3, ***P
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