title: Expression of functional TRPA1 receptor on human lung fibroblast and epithelial cells.
abstract: The transient receptor potential subfamily A member 1 (TRPA1) is a non-selective cation channel implicated in the pathogenesis of several airway diseases like asthma and chronic obstructive pulmonary disease (COPD). Most of the research on TRPA1 focuses on its expression and function in neuronal context; studies investigating non-neuronal expression of TRPA1 are lacking. In the present study, we show functional expression of TRPA1 in human lung fibroblast cells (CCD19-Lu) and human pulmonary alveolar epithelial cell line (A549). We demonstrate TRPA1 expression at both mRNA and protein levels in these cell types. TRPA1 selective agonists like allyl isothiocyanate (AITC), 4-hydroxynonenal (4-HNE), crotonaldehyde and zinc, induced a concentration-dependent increase in Ca+2 influx in CCD19-Lu and A549 cells. AITC-induced Ca+2 influx was inhibited by Ruthenium red (RR), a TRP channel pore blocker, and by GRC 17536, a TRPA1 specific antagonist. Furthermore, we also provide evidence that activation of the TRPA1 receptor by TRPA1 selective agonists promotes release of the chemokine IL-8 in CCD19-Lu and A549 cells. The IL-8 release in response to TRPA1 agonists was attenuated by TRPA1 selective antagonists. In conclusion, we demonstrate here for the first time that TRPA1 is functionally expressed in cultured human lung fibroblast cells (CCD19-Lu) and human alveolar epithelial cell line (A549) and may have a potential role in modulating release of this important chemokine in inflamed airways.
authors.affiliation: Biological Research, Glenmark Pharmaceuticals Ltd., Glenmark Research Centre, Navi Mumbai, Maharashtra, India.
authors.forename: Indranil
authors.initials: I
authors.lastname: Mukhopadhyay
authors.forename: Pearl
authors.initials: P
authors.lastname: Gomes
authors.forename: Sarika
authors.initials: S
authors.lastname: Aranake
authors.forename: Mahesh
authors.initials: M
authors.lastname: Shetty
authors.forename: Pallavi
authors.initials: P
authors.lastname: Karnik
authors.forename: Madhujit
authors.initials: M
authors.lastname: Damle
authors.forename: Shaldavya
authors.initials: S
authors.lastname: Kuruganti
authors.forename: Sandeep
authors.initials: S
authors.lastname: Thorat
authors.forename: Neelima
authors.initials: N
authors.lastname: Khairatkar-Joshi
mesh_terms: D000447:Aldehydes / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002413:Cations, Divalent / Q000378:metabolism; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000187:drug effects / Q000378:metabolism*; D017879:Isothiocyanates / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012430:Ruthenium Red / Q000494:pharmacology; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017967:Zinc Compounds / Q000494:pharmacology
chemical_list: D000447:Aldehydes; D015220:Calcium Channels; D002413:Cations, Divalent; D002712:Chlorides; D016209:Interleukin-8; D017879:Isothiocyanates; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; D017967:Zinc Compounds; D012430:Ruthenium Red; C016837:zinc chloride; C012796:2-butenal; C004471:allyl isothiocyanate; C027576:4-hydroxy-2-nonenal; D002118:Calcium