{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T22:19:53Z","timestamp":1787523593430,"version":"build-2736575974"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"<jats:p>\n                    Environmental exposure to airway irritants can elicit sensory irritation and contribute to various disease outcomes. Although\n                    <jats:italic>in vitro<\/jats:italic>\n                    assays have been developed to measure skin and eye irritation, evaluation of respiratory sensory irritation relies predominately on\n                    <jats:italic>in vivo<\/jats:italic>\n                    testing using the RD\n                    <jats:sub>50<\/jats:sub>\n                    assay, or Alarie test. Although the RD\n                    <jats:sub>50<\/jats:sub>\n                    assay aligns well with human responses, various disadvantages, such as low throughput and interspecies differences in receptors responsible for detecting noxious stimuli, highlights a few of the many requirements for alternative, or complementary\n                    <jats:italic>in vitro<\/jats:italic>\n                    approaches. Recently, increased emphasis has been placed on methods that predict human responses at the mechanistic level. In this study, we have developed a human relevant\n                    <jats:italic>in vitro<\/jats:italic>\n                    model for airway irritant detection based around molecular events of airway irritation, including transient receptor potential channel activation and substance P release. Using alveolar- and bronchial-derived cell lines, we demonstrate endogenous TRPA1-driven Substance P release following exposure to prototypical irritants. Calcium response was confirmed by flow cytometry following exposure to irritants, with substance P release demonstrated at both the gene and protein levels by qPCR, immunocytochemistry and ELISA. Furthermore, our model demonstrates some concordance with\n                    <jats:italic>in vivo<\/jats:italic>\n                    RD\n                    <jats:sub>50<\/jats:sub>\n                    data.\n                  <\/jats:p>","DOI":"10.3389\/ftox.2026.1870419","type":"journal-article","created":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T22:10:19Z","timestamp":1787523019000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A TRPA1-mediated substance P release assay as an in vitro screening tool for airway irritant potential"],"prefix":"10.3389","volume":"8","author":[{"given":"R.","family":"Bedford","sequence":"first","affiliation":[{"name":"Labcorp","place":["Harrogate, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Medhane","sequence":"additional","affiliation":[{"name":"Labcorp","place":["Harrogate, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Lawrance","sequence":"additional","affiliation":[{"name":"Labcorp","place":["Harrogate, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Hollings","sequence":"additional","affiliation":[{"name":"Labcorp","place":["Harrogate, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2035","DOI":"10.1007\/s10571-022-01284-7","article-title":"Substance P reduces infarct size and mortality after ischemic stroke, possibly through the M2 polarization of microglia\/macrophages and neuroprotection in the ischemic rat brain","volume":"43","author":"Ahn","year":"2023","journal-title":"Cell Mol. 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