External stimuli such as cigarette smoke and house dust mite are often involved in the development and exacerbation of asthma. These risk factors could activate or sensitize transient receptor potential channel ankyrin 1 (TRPA1), which are primarily expressed in neuronal structures but also in non-neuronal cells such as fibroblasts. However, the role of non-neuronal TRPA1 in the pathophysiology of airway diseases including asthma remains unclear. We investigated TRPA1 expression on human fibroblast cells and whether inflammatory mediators could modulate its function. This study utilized human lung fibroblast cell lines, Medical Research Council cell strain 5 (MRC-5) and HF19 cells frequently used on experimental studies regarding allergic and respiratory disorders. The human lung fibroblasts were stimulated with house dust mite (Der p1) or tumor necrosis factor alpha (TNF-α) for 24 h, and we quantified TRPA1 mRNA and protein by qRT-PCR and western blot analysis, respectively. TRPA1 mRNA expressions were upregulated after TNF-α treatment. Calcium imaging analysis revealed that TNF-α treatment apparently sensitized TRPA1-mediated calcium influx by TRPA1 agonist allyl isothiocyanate (AITC) and the selective TRPA1 channel blocker HC-030031 effectively reduced the calcium response. Lastly, TRPA1 activation was not only involved in increased IL-8 cytokine release, but also in upregulating gene expression of matrix metalloprotease 9 (MMP9) in the human lung fibroblasts treated with TNF-α Together, these results indicate that presence of inflammatory mediators such as TNF-α could upregulate the non-neuronal expression of TRPA1 on fibroblasts which may aggravate further the release of inflammatory cytokines observed in human airway diseases.Copyright © 2020. Published by Elsevier Ltd.
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