{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:49:08Z","timestamp":1787017748379,"version":"build-2736575974"},"reference-count":65,"publisher":"Wiley","license":[{"start":{"date-parts":[[2019,2,17]],"date-time":"2019-02-17T00:00:00Z","timestamp":1550361600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 HL088594"],"award-info":[{"award-number":["P01 HL088594"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1UL1 TR002373"],"award-info":[{"award-number":["1UL1 TR002373"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 HL088594"],"award-info":[{"award-number":["P01 HL088594"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1UL1 TR002373"],"award-info":[{"award-number":["1UL1 TR002373"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2019,2,17]]},"abstract":"<jats:p>\n                    Asthma is often associated with airway eosinophilia, and therapies targeting eosinophils are now available to treat severe eosinophilic asthma. Eosinophilic asthma is often due to a type-2 immune response and production of IL-5, which leads to eosinophilopiesis and recruitment of mature eosinophils in the airways. A concomitant type-2 and type-17 response has been reported in some individuals. IL-17 may be enhanced by IL-1\n                    <jats:italic>\u03b2<\/jats:italic>\n                    production and can lead to neutrophilic inflammation. In fact, both eosinophilic and neutrophilic (mixed granulocytic) inflammation are simultaneously present in a large population of patients with asthma. In monocyte\/macrophage cell populations, release of mature IL-1\n                    <jats:italic>\u03b2<\/jats:italic>\n                    occurs via toll-like receptor ligand-induced activation of the inflammasome. Within the inflammasome, a cascade of events leads to the activation of caspase-1, which cleaves pro-IL-1\n                    <jats:italic>\u03b2<\/jats:italic>\n                    protein into a mature, releasable, and active form. We have demonstrated that eosinophils can release IL-1\n                    <jats:italic>\u03b2<\/jats:italic>\n                    in a Toll-like receptor ligand-independent fashion. The objective of this study was to determine the mechanisms underlying the production and maturation of IL-1\n                    <jats:italic>\u03b2<\/jats:italic>\n                    in cytokine-activated eosinophils. Using eosinophils from circulating blood and from bronchoalveolar lavage fluid after an airway allergen challenge, the present study demonstrates that cytokine-activated eosinophils express and release a bioactive form of IL-1\n                    <jats:italic>\u03b2<\/jats:italic>\n                    with an apparent size less than the typical 17\u2009kDa mature form produced by macrophages. Using a zymography approach and pharmacological inhibitors, we identified matrix metalloproteinase-9 (MMP-9) as a protease that cleaves pro-IL-1\n                    <jats:italic>\u03b2<\/jats:italic>\n                    into a ~15\u2009kDa form and allows the release of IL-1\n                    <jats:italic>\u03b2<\/jats:italic>\n                    from cytokine-activated eosinophils. Therefore, we conclude that activated eosinophils produce MMP-9, which causes the release of IL-1\n                    <jats:italic>\u03b2<\/jats:italic>\n                    in an inflammasome\/caspase-1-independent manner. The production of IL-1\n                    <jats:italic>\u03b2<\/jats:italic>\n                    by eosinophils may be a link between the eosinophilic\/type-2 immune response and the neutrophilic\/type-17 immune response that is often associated with a more severe and treatment-refractory type of asthma.\n                  <\/jats:p>","DOI":"10.1155\/2019\/7479107","type":"journal-article","created":{"date-parts":[[2019,2,17]],"date-time":"2019-02-17T18:31:13Z","timestamp":1550428273000},"page":"1-11","source":"Crossref","is-referenced-by-count":34,"title":["Matrix Metalloproteinase-9-Dependent Release of IL-1\n                    <i>\u03b2<\/i>\n                    by Human Eosinophils"],"prefix":"10.1155","volume":"2019","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7238-8671","authenticated-orcid":true,"given":"Stephane","family":"Esnault","sequence":"first","affiliation":[{"name":"University of Wisconsin-Madison School of Medicine and Public Health, Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Kelly","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison School of Medicine and Public Health, Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean H.","family":"Johnson","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison School of Medicine and Public Health, Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa P.","family":"DeLain","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison School of Medicine and Public Health, Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline J.","family":"Haedt","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison School of Medicine and Public Health, Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea L.","family":"Noll","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison School of Medicine and Public Health, Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Sandbo","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison School of Medicine and Public Health, Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nizar N.","family":"Jarjour","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison School of Medicine and Public Health, Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Madison, WI, 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