{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:02:47Z","timestamp":1791428567977,"version":"4.3.3"},"reference-count":55,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T00:00:00Z","timestamp":1668211200000},"content-version":"am","delay-in-days":331,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CHE\u201003\u201042251"],"award-info":[{"award-number":["CHE\u201003\u201042251"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CHE\u201090\u201013145"],"award-info":[{"award-number":["CHE\u201090\u201013145"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL081873"],"award-info":[{"award-number":["R01HL081873"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008925","name":"American Asthma Foundation","doi-asserted-by":"publisher","award":["12\u20100049"],"award-info":[{"award-number":["12\u20100049"]}],"id":[{"id":"10.13039\/100008925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PP2\u2010133388"],"award-info":[{"award-number":["PP2\u2010133388"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP\u20106254"],"award-info":[{"award-number":["MOP\u20106254"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>The 5\u2010lipoxygenase product, 5\u2010oxo\u2010ETE (5\u2010oxo\u20106,8,11,14\u2010eicosatetraenoic acid), is a potent chemoattractant for eosinophils and neutrophils. However, little is known about its pathophysiological role because of the lack of a rodent ortholog of the oxoeicosanoid (OXE) receptor. The present study aimed to determine whether the selective OXE receptor antagonist <jats:bold><jats:italic>S<\/jats:italic>\u2010Y048<\/jats:bold> can inhibit allergen\u2010induced pulmonary inflammation in a monkey model of asthma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Monkeys sensitized to house dust mite antigen (HDM) were treated with either vehicle or <jats:bold><jats:italic>S<\/jats:italic>\u2010Y048<\/jats:bold> prior to challenge with aerosolized HDM, and bronchoalveolar (BAL) fluid was collected 24\u2009h later. After 6\u00a0weeks, animals that had initially been treated with vehicle received <jats:bold><jats:italic>S<\/jats:italic>\u2010Y048<\/jats:bold> and vice versa for animals initially treated with <jats:bold><jats:italic>S<\/jats:italic>\u2010Y048<\/jats:bold>. Eosinophils and neutrophils in BAL and lung tissue samples were evaluated, as well as mucus\u2010containing cells in bronchi.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>HDM significantly increased the numbers of eosinophils, neutrophils, and macrophages in BAL fluid 24\u2009h after challenge. These responses were all significantly inhibited by <jats:bold><jats:italic>S<\/jats:italic>\u2010Y048<\/jats:bold>, which also reduced the numbers of eosinophils and neutrophils in lung tissue 24\u2009h after challenge with HDM. <jats:bold><jats:italic>S<\/jats:italic>\u2010Y048<\/jats:bold> also significantly reduced the numbers of bronchial epithelial cells staining for mucin and MUC5AC after antigen challenge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>This study provides the first evidence that 5\u2010oxo\u2010ETE may play an important role in inducing allergen\u2010induced pulmonary inflammation and could also be involved in regulating MUC5AC in goblet cells. OXE receptor antagonists such as <jats:bold><jats:italic>S<\/jats:italic>\u2010Y048<\/jats:bold> may useful therapeutic agents in asthma and other eosinophilic as well as neutrophilic diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15721","type":"journal-article","created":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T09:54:27Z","timestamp":1636710867000},"page":"322-336","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Targeting the OXE receptor with a selective antagonist inhibits allergen\u2010induced pulmonary inflammation in non\u2010human primates"],"prefix":"10.1111","volume":"179","author":[{"given":"Chantal","family":"Cossette","sequence":"first","affiliation":[{"name":"Meakins\u2010Christie Laboratories, Centre for Translational Biology McGill University Health Centre  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Miller","sequence":"additional","affiliation":[{"name":"California National Primate Research Center University of California  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3812-3001","authenticated-orcid":false,"given":"Qiuji","family":"Ye","sequence":"additional","affiliation":[{"name":"Claude Pepper Institute and Department of Chemistry Florida Institute of Technology  Melbourne Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2629-9632","authenticated-orcid":false,"given":"Shishir","family":"Chourey","sequence":"additional","affiliation":[{"name":"Claude Pepper Institute and Department of Chemistry Florida Institute of Technology  Melbourne Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chintam Nagendra","family":"Reddy","sequence":"additional","affiliation":[{"name":"Claude Pepper Institute and Department of Chemistry Florida Institute of Technology  Melbourne Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1814-7505","authenticated-orcid":false,"given":"Joshua","family":"Rokach","sequence":"additional","affiliation":[{"name":"Claude Pepper Institute and Department of Chemistry Florida Institute of Technology  Melbourne Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8507-4038","authenticated-orcid":false,"given":"William S.","family":"Powell","sequence":"additional","affiliation":[{"name":"Meakins\u2010Christie Laboratories, Centre for Translational Biology McGill University Health Centre  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,16]]},"reference":[{"issue":"1","key":"e_1_2_12_2_1","first-page":"S27","article-title":"The concise guide to pharmacology 2021\/22: G protein\u2010coupled receptors","volume":"178","author":"Alexander S. P.","year":"2021","journal-title":"British Journal of Pharmacology"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12665"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm6120112"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.10.5948"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050901"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b00895"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2015.05.009"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14153"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.03.00102002"},{"key":"e_1_2_12_12_1","doi-asserted-by":"crossref","first-page":"4315","DOI":"10.4049\/jimmunol.140.12.4315","article-title":"Human granulocyte\u2010macrophage colony\u2010stimulating factor and other cytokines prime human neutrophils for enhanced arachidonic acid release and leukotriene B4 synthesis","volume":"140","author":"DiPersio J. F.","year":"1988","journal-title":"Journal of Immunology"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-1676.1996.tb02086.x"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2818"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401294200"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm401292m"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2009.04.016"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.02.010"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/00401706.1969.10490657"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.21.1.3517"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M203194200"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2005.04.029"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.63.3.471"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep44418"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.1940.sp000825"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12990"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200509-1412OC"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/21658"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2017.00093"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14872"},{"key":"e_1_2_12_32_1","first-page":"340","article-title":"Neutrophils and asthma","volume":"19","author":"Monteseirin J.","year":"2009","journal-title":"Journal of Investigational Allergology & Clinical Immunology"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mcp.0000198064.27586.37"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(03)01888-8"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.30.17821"},{"key":"e_1_2_12_36_1","doi-asserted-by":"crossref","first-page":"336","DOI":"10.4049\/jimmunol.157.1.336","article-title":"5\u2010Oxo\u2010eicosatetraenoate is a broadly active, eosinophil\u2010selective stimulus for human granulocytes","volume":"157","author":"O'Flaherty J. T.","year":"1996","journal-title":"Journal of Immunology"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201804-0734OC"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809120105"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.4.1225"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20190657"},{"key":"e_1_2_12_42_1","doi-asserted-by":"crossref","first-page":"4123","DOI":"10.4049\/jimmunol.154.8.4123","article-title":"5\u2010Oxo\u20106,8,11,14\u2010eicosatetraenoic acid is a potent stimulator of human eosinophil migration","volume":"154","author":"Powell W. S.","year":"1995","journal-title":"Journal of Immunology"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)98347-X"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)41766-8"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.113930"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.1980.tb01782.x"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63973-9"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2000.00953.x"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)42302-2"},{"key":"e_1_2_12_50_1","doi-asserted-by":"crossref","first-page":"4664","DOI":"10.4049\/jimmunol.157.10.4664","article-title":"Stimulating properties of 5\u2010oxo\u2010eicosanoids for human monocytes: Synergism with monocyte chemotactic protein\u20101 and \u20103","volume":"157","author":"Sozzani S.","year":"1996","journal-title":"Journal of Immunology"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401537200"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2005.08.001"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.50.2.140"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2017.00158"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.2220\/biomedres.23.101"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14874"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.15721","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.15721","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/am-pdf\/10.1111\/bph.15721","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.15721","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T15:17:51Z","timestamp":1692976671000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.15721"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,16]]},"references-count":55,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1111\/bph.15721"],"URL":"https:\/\/doi.org\/10.1111\/bph.15721","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,16]]},"assertion":[{"value":"2021-04-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}