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The IL-6-type cytokine Oncostatin M (OSM) elevates lung inflammation, Th2-skewed cytokines, alternatively activated (M2) macrophages, and eosinophils in C57Bl\/6 mice in vivo. Since OSM induces IL-33 expression, we here test the IL-33 function in OSM-mediated lung inflammation using IL-33-\/- mice. Adenoviral OSM (AdOSM) markedly induced IL-33 mRNA and protein levels in wild-type animals while IL-33 was undetectable in IL-33-\/- animals. AdOSM treatment showed recruitment of neutrophils, eosinophils, and elevated inflammatory chemokines (KC, eotaxin-1, MIP1a, and MIP1b), Th2 cytokines (IL-4\/IL-5), and arginase-1 (M2 macrophage marker) whereas these responses were markedly diminished in IL-33-\/- mice. AdOSM-induced IL-33 was unaffected by IL-6-\/- deficiency. AdOSM also induced IL-33R+ ILC2 cells in the lung, while IL-6 (AdIL-6) overexpression did not. Flow-sorted ILC2 responded in vitro to IL-33 (but not OSM or IL-6 stimulation). Matrix remodelling genes col3A1, MMP-13, and TIMP-1 were also decreased in IL-33-\/- mice. In vitro, IL-33 upregulated expression of OSM in the RAW264.7 macrophage cell line and in bone marrow-derived macrophages. Taken together, IL-33 is a critical mediator of OSM-driven, Th2-skewed, and M2-like responses in mouse lung inflammation and contributes in part through activation of ILC2 cells.<\/jats:p>","DOI":"10.1155\/2020\/4087315","type":"journal-article","created":{"date-parts":[[2020,11,28]],"date-time":"2020-11-28T16:50:05Z","timestamp":1606582205000},"page":"1-17","source":"Crossref","is-referenced-by-count":18,"title":["IL-33 Mediates Lung Inflammation by the IL-6-Type Cytokine Oncostatin M"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7226-5521","authenticated-orcid":true,"given":"Fernando","family":"Botelho","sequence":"first","affiliation":[{"name":"McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, L8N 3Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anisha","family":"Dubey","sequence":"additional","affiliation":[{"name":"McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, L8N 3Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehab A.","family":"Ayaub","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rex","family":"Park","sequence":"additional","affiliation":[{"name":"McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, L8N 3Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Yip","sequence":"additional","affiliation":[{"name":"McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, L8N 3Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Humbles","sequence":"additional","affiliation":[{"name":"Early RIA, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB4 0WG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Kolbeck","sequence":"additional","affiliation":[{"name":"Early RIA, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0081-2231","authenticated-orcid":true,"given":"Carl D.","family":"Richards","sequence":"additional","affiliation":[{"name":"McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, L8N 3Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.07.007"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.4.2551"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200940291"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.06.006"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3370"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2010.04.005"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.7.4780"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.02.013"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00692"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0088714"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20112691"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-014-1447-9"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.534396"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/9858374"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002296200"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/512103"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1111\/sji.12694"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.10.7243"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903476"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1203318"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.1035"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2014.81"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-13511-z"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1038\/srep34255"},{"issue":"6","key":"25","first-page":"942","article-title":"Short technical reports. 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