The following is a summary of “TRPV2 modulates mechanically Induced ATP Release from Human bronchial epithelial cells,” published in the April 2024 issue of Pulmonology by Dunne et al.

Repetitive coughing episodes exert significant shear stress on the large airways, triggering the release of alarmins and adenosine triphosphate (ATP), a tussive agent. The activity of ion channels within the human airway potentially modulates this process. This study aimed to explore the involvement of the transient receptor potential subfamily vanilloid member 2 (TRPV2) channel in mechanically induced ATP release from primary bronchial epithelial cells (PBECs).

Primary bronchial epithelial cells were cultured from individuals undergoing bronchoscopy and subjected to compressive and fluid shear stress (CFSS) or fluid shear stress (FSS) alone at various intensities to induce mechanical stress. ATP release was quantified using a luciferin–luciferase assay. Confocal calcium imaging confirmed the presence of functional TRPV2 protein expression in human PBECs. The impact of TRPV2 inhibition on FSS-induced ATP release was investigated using the TRPV2 inhibitor tranilast or TRPV2 siRNA knockdown. Immunohistochemistry analysis of human lung tissue revealed TRPV2 protein expression.

CFSS significantly elevated ATP release in PBECs compared to unstimulated cells, indicating a mechanosensitive response (***P < 0.001). PBECs exhibited functional TRPV2 channels, and TRPV2 protein expression was detected in human lung tissue. Inhibition of TRPV2 using tranilast or siRNA knockdown decreased ATP release from FSS-stimulated PBECs (**P < 0.01 and *P < 0.05, respectively), further implicating TRPV2 in the modulation of ATP release in response to mechanical stress.

In summary, this study demonstrates the expression of TRPV2 channels in the human airway and their involvement in the regulation of mechanically induced ATP release from PBECs. These findings shed light on the mechanosensitive mechanisms underlying ATP release in airway epithelial cells and may have implications for understanding airway pathophysiology and developing targeted therapies for conditions such as cough and airway inflammation.

Source: respiratory-research.biomedcentral.com/articles/10.1186/s12931-024-02807-0