{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T23:00:02Z","timestamp":1793055602204,"version":"4.5.0"},"reference-count":46,"publisher":"BMJ","issue":"8","funder":[{"DOI":"10.13039\/501100003621","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Thorax"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Respiratory fungal exposure is known to be associated with severe allergic lung inflammation. Airway epithelium is an essential controller of allergic inflammation. An innate immune recognition receptor, nucleotide-binding domain, leucine-rich-containing family, pyrin-domain-containing-3 (NLRP3) inflammasome, and phosphoinositide 3 kinase (PI3K)-\u03b4 in airway epithelium are involved in various inflammatory processes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We investigated the role of NLRP3 inflammasome in fungi-induced allergic lung inflammation and examined the regulatory mechanism of NLRP3 inflammasome, focusing on PI3K-\u03b4 in airway epithelium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used two in vivo models induced by exposure to <jats:italic>Aspergillus fumigatus<\/jats:italic> (<jats:italic>Af<\/jats:italic>) and <jats:italic>Alternaria alternata<\/jats:italic> (<jats:italic>Aa<\/jats:italic>), as well as an <jats:italic>Af<\/jats:italic>-exposed in vitro system. We also checked NLRP3 expression in lung tissues from patients with allergic bronchopulmonary aspergillosis (ABPA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Assembly\/activation of NLRP3 inflammasome was increased in the lung of <jats:italic>Af<\/jats:italic>-exposed mice. Elevation of NLRP3 inflammasome assembly\/activation was observed in <jats:italic>Af<\/jats:italic>-stimulated murine and human epithelial cells. Similarly, pulmonary expression of NLRP3 in patients with ABPA was increased. Importantly, neutralisation of NLRP3 inflammasome derived IL-1\u03b2 alleviated pathophysiological features of <jats:italic>Af<\/jats:italic>-induced allergic inflammation. Furthermore, PI3K-\u03b4 blockade improved <jats:italic>Af<\/jats:italic>-induced allergic inflammation through modulation of NLRP3 inflammasome, especially in epithelial cells. This modulatory role of PI3K-\u03b4 was mediated through the regulation of mitochondrial reactive oxygen species (mtROS) generation. NLRP3 inflammasome was also implicated in <jats:italic>Aa<\/jats:italic>-induced eosinophilic allergic inflammation, which was improved by PI3K-\u03b4 blockade.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings demonstrate that fungi-induced assembly\/activation of NLRP3 inflammasome in airway epithelium may be modulated by PI3K-\u03b4, which is mediated partly through the regulation of mtROS generation. Inhibition of PI3K-\u03b4 may have potential for treating fungi-induced severe allergic lung inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1136\/thoraxjnl-2017-210326","type":"journal-article","created":{"date-parts":[[2018,4,5]],"date-time":"2018-04-05T22:47:11Z","timestamp":1522968431000},"page":"758-768","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["Airway epithelial phosphoinositide 3-kinase-\u03b4 contributes to the modulation of fungi-induced innate immune response"],"prefix":"10.1136","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4635-8302","authenticated-orcid":false,"given":"Jae Seok","family":"Jeong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Bae","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So 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