{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T21:07:20Z","timestamp":1776719240477,"version":"3.51.2"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pulm Med"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Oroscomucoid 3 (ORMDL3) has been linked to susceptibility of childhood asthma and respiratory viral infection. Polyinosinic-polycytidylic acid (poly I:C) is a synthetic analog of viral double-stranded RNA, a toll-like receptor 3 (TLR3) ligand and mimic of viral infection.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>To investigate the functional role of ORMDL3 in the poly I:C-induced inflammatory response in airway epithelial cells, <jats:italic>ORMDL3<\/jats:italic> knockdown and over-expression models were established in human  A549\u00a0epithelial cells and primary normal human bronchial epithelial (NHBE) cells. The cells were stimulated with poly I:C or the Th17 cytokine IL-17A. IL-6 and IL-8 levels in supernatants,\u00a0 mRNA levels of genes in the TLR3 pathway and inflammatory response from cell pellets\u00a0were measured. <jats:italic>ORMDL3<\/jats:italic> knockdown models in A549 and BEAS-2B epithelial cells were then infected with live human rhinovirus (HRV16) followed by IL-6 and IL-8 measurement.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p><jats:italic>ORMDL3<\/jats:italic> knockdown and over-expression had little influence on the transcript levels of <jats:italic>TLR3<\/jats:italic> in airway epithelial cells. Time course studies showed that <jats:italic>ORMDL3<\/jats:italic>-deficient A549 and NHBE cells had an attenuated IL-6 and IL-8 response to poly I:C stimulation. A549 and NHBE cells over-expressing <jats:italic>ORMDL3<\/jats:italic> released relatively more IL-6 and IL-8 following poly I:C stimulation. IL-17A exhibited a similar inflammatory response in <jats:italic>ORMDL3<\/jats:italic> knockdown and over-expressing cells, but co-stimulation of poly I:C and IL-17A did not significantly enhance the IL-6 and IL-8 response. Transcript abundance of <jats:italic>IFNB<\/jats:italic> following poly I:C stimulation was not significantly altered by <jats:italic>ORMDL3<\/jats:italic> knockdown or over-expression. Dampening of the IL-6 response by <jats:italic>ORMDL3<\/jats:italic> knockdown was confirmed in HRV16 infected BEAS-2B and A549 cells.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>ORMDL3 regulates the viral inflammatory response in airway epithelial cells via mechanisms independent of the TLR3 pathway.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12890-021-01496-5","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T09:02:23Z","timestamp":1621242143000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["ORMDL3 regulates poly I:C induced inflammatory responses in airway epithelial cells"],"prefix":"10.1186","volume":"21","author":[{"given":"Gemma","family":"Laura","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kieran","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saffron A. 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