{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T01:42:49Z","timestamp":1787881369080,"version":"build-2784847793"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,12,21]],"date-time":"2015-12-21T00:00:00Z","timestamp":1450656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1026880"],"award-info":[{"award-number":["APP1026880"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1025637"],"award-info":[{"award-number":["APP1025637"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>IL\u201017A plays an important role in respiratory disease and is a known regulator of pulmonary inflammation and immunity. Recent studies have linked IL\u201017A with exacerbation in asthma and COPD. We have shown that the enzyme cyclooxygenase\u20102 (COX\u20102) and its prostanoid products, prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>) in particular, are key contributors in <jats:italic>in vitro<\/jats:italic> models of infectious exacerbation; however, the impact of IL\u201017A was not known.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>We address this herein and show that IL\u201017A induces a robust and sustained upregulation of COX\u20102 protein and PGE<jats:sub>2<\/jats:sub> secretion from airway smooth muscle (ASM) cells. COX\u20102 can be regulated at transcriptional, post\u2010transcriptional and\/or post\u2010translational levels. We have elucidated the underlying molecular mechanisms responsible for the sustained upregulation of TNF\u2010\u03b1\u2010induced COX\u20102 by IL\u201017A in ASM cells and show that is not via increased COX\u20102 gene expression. Instead, TNF\u2010\u03b1\u2010induced COX\u20102 upregulation is subject to regulation by the proteasome, and IL\u201017A acts to increase TNF\u2010\u03b1\u2010induced COX\u20102 protein stability as confirmed by cycloheximide chase experiments. In this way, IL\u201017A acts to amplify the COX\u20102\u2010mediated effects of TNF\u2010\u03b1 and greatly enhances PGE<jats:sub>2<\/jats:sub> secretion from ASM cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>As PGE<jats:sub>2<\/jats:sub> is a multifunctional prostanoid with diverse roles in respiratory disease, our studies demonstrate a novel function for IL\u201017A in airway inflammation by showing for the first time that IL\u201017A impacts on the COX\u20102\/PGE<jats:sub>2<\/jats:sub> pathway, molecules known to contribute to disease exacerbation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.12810","type":"journal-article","created":{"date-parts":[[2015,11,25]],"date-time":"2015-11-25T21:24:51Z","timestamp":1448486691000},"page":"387-396","source":"Crossref","is-referenced-by-count":20,"title":["IL\u201017A increases TNF\u2010\u03b1\u2010induced COX\u20102 protein stability and augments PGE<sub>2<\/sub> secretion from airway smooth muscle cells: impact on \u03b2<sub>2<\/sub>\u2010adrenergic receptor desensitization"],"prefix":"10.1111","volume":"71","author":[{"given":"N. N.","family":"Rumzhum","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy University of Sydney Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. S.","family":"Patel","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy University of Sydney Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Prabhala","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy University of Sydney Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. C.","family":"Gelissen","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy University of Sydney Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. G.","family":"Oliver","sequence":"additional","affiliation":[{"name":"Woolcock Institute of Medical Research University of Sydney Sydney NSW Australia"},{"name":"School of Life Sciences University of Technology Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. J.","family":"Ammit","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy University of Sydney Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,12,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201405-0859PP"},{"key":"e_1_2_8_3_1","first-page":"397","article-title":"Cytokine inhibition in the treatment of COPD","volume":"9","author":"Caramori G","year":"2014","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12183"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.06.048"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002244"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201409-1689OC"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402529"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0126OC"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056058"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.12449"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2014\u20100443OC"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/645383"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1006\/pulp.1995.1006"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701152"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2007.01.001"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.304220"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1999.1646"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.07.123"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2010.11.018"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2009.12.007"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00317.2011"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.23.6.4184"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3020723"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.12.4265-4274.2000"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M710137200"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.6.4135"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.06.023"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00367.2005"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608281200"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4432"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00562439"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)90409-3"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2012.05.007"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1569-9048(03)00146-0"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)06128-5"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.02088.x"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00061614"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2014-206592"}],"container-title":["Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fall.12810","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.12810","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T06:14:55Z","timestamp":1696486495000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/all.12810"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,21]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["10.1111\/all.12810"],"URL":"https:\/\/doi.org\/10.1111\/all.12810","archive":["Portico"],"relation":{},"ISSN":["0105-4538","1398-9995"],"issn-type":[{"value":"0105-4538","type":"print"},{"value":"1398-9995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,21]]}}}