Functional expression of the transient receptor potential channel TRPA1, a sensor for toxic lung inhalants, in pulmonary epithelial cells

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…The TRPA1 agonist allyl-isothiocyanate evokes Ca 2+ currents in small cell carcinoma cells and promotes the survival of tumor cells via ERK phosphorylation. TRPA1 is expressed in airway epithelial cells, where it serves as a receptor for toxic lung inhalants, many of which are carcinogenic (Büch et al, 2013). Thus, one might speculate that TRPA1 is instrumental for both the initiation and progression of lung cancer.…”

The emerging role of transient receptor potential channels in chronic lung disease

“…In the lung, TRPV1 expression has been found in human bronchial epithelial cells with an increase in expression in cells from the airways of patients with refractory asthma [99][100][101][102][103][104][105]109], fibroblasts [102], T-cells [106,107,115] and human alveolar macrophages [99]. Several studies suggest that TRPV1 channel activation evokes the release of proinflammatory cytokines and ATP from bronchial epithelial cells [99,[103][104][105]116].…”

“…Although TRPA1 is predominantly expressed in sensory nociceptive neurons, TRPA1 gene expression has been demonstrated in non-neuronal cells, including epithelial, fibroblasts, B-cells, airway smooth muscle, CD4 + and CD8 + T-cells [108,109,110,124]. A role for TRPA1 has been demonstrated in murine models of allergic asthma utilising small molecule antagonists and TRPA1 −/− mice with an inhibitory effect on inflammatory mediator and mucus production, leukocyte infiltration and airway hyperresponsiveness (AHR) to acetylcholine [118].…”

Cold stress increases reactive oxygen species formation via TRPA1 activation in A549 cells

“…Our results suggest that TRPA1 is mainly involved in the production of ROS via [Ca 2+ ] c elevation pathway induced by cold stress in lung epithelial cell. The pulmonary expression of TRPA1 has been found in sensory nerve endings and pulmonary epithelial cells, which is involved in the acceleration of inflammatory responses in the lung (Büch et al 2013). On the other hand, ROS are important components of signaling cascades that respond to extracellular stimuli, including tumor necrosis factor, interleukin-1, adenosine-5′-triphosphate, cigarette smoke extract, lipoteichoic acid, or lipopolysaccharide, which are associated with many of the known inflammatory target proteins, such as metalloproteinase-9, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, cyclooxygenase-2, and cytosolic phospholipase A2.…”

“…TRPA1 protein has been found in the airway epithelial cells toward the air in the human lung (Büch et al 2013). The previous research has reported TRPA1 expression at mRNA and protein levels in A549 cell line (Mukhopadhyay et al 2011).…”