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Airway epithelial cells (AECs) play a critical role in this process by sensing the proteolytic activity of allergens via protease-activated receptors (PAR2) to initiate inflammatory and immune responses in the airway. Elevation of cytosolic Ca<jats:sup>2+<\/jats:sup>is an important signaling event in this process, yet the fundamental mechanism by which allergens induce Ca<jats:sup>2+<\/jats:sup>elevations in AECs remains poorly understood. Here we find that extracts from dust mite and cockroach induce sustained Ca<jats:sup>2+<\/jats:sup>elevations in AECs through the activation of Ca<jats:sup>2+<\/jats:sup>release-activated Ca<jats:sup>2+<\/jats:sup>(CRAC) channels encoded by Orai1 and STIM1. CRAC channel activation occurs, at least in part, through allergen mediated stimulation of PAR2 receptors. The ensuing Ca<jats:sup>2+<\/jats:sup>entry then activates NFAT\/calcineurin signaling to induce transcriptional production of the proinflammatory cytokines IL-6 and IL-8. These findings highlight a key role for CRAC channels as regulators of allergen induced inflammatory responses in the airway.<\/jats:p>","DOI":"10.1038\/srep32311","type":"journal-article","created":{"date-parts":[[2016,9,8]],"date-time":"2016-09-08T08:59:03Z","timestamp":1473325143000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Allergens stimulate store-operated calcium entry and cytokine production in airway epithelial cells"],"prefix":"10.1038","volume":"6","author":[{"given":"Amit","family":"Jairaman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea H.","family":"Maguire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Schleimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murali","family":"Prakriya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,9,8]]},"reference":[{"key":"BFsrep32311_CR1","doi-asserted-by":"publisher","first-page":"147","DOI":"10.3389\/fimmu.2015.00147","volume":"6","author":"VD Gandhi","year":"2015","unstructured":"Gandhi, V. 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