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IL\u201036\u03b1, IL\u201036\u03b2 and IL\u201036\u03b3, which belong to the extended IL\u20101 family, have been implicated as key initiators of skin inflammation in psoriasis. IL\u201036\u03b3 is highly upregulated in lesional skin from psoriatic individuals, and heritable mutations in the natural IL\u201036 receptor antagonist result in a severe form of psoriasis. IL\u201036 family cytokines are initially expressed as inactive precursors that require proteolytic processing for activation. The neutrophil granule\u2010derived protease elastase proteolytically processes and activates IL\u201036\u03b1 and IL\u201036\u03b3, increasing their biological activity ~ 500\u2010fold, and also robustly activates IL\u20101\u03b1 and IL\u201033 through limited proteolytic processing. Consequently, inhibitors of elastase activity may have potential as anti\u2010inflammatory agents through antagonizing the activation of multiple IL\u20101 family cytokines. Using <jats:italic>in silico<\/jats:italic> screening approaches, we have identified small\u2010molecule inhibitors of elastase that can antagonize activation of IL\u201036\u03b3 by the latter protease. The compounds reported herein may have utility as lead compounds for the development of inhibitors of elastase\u2010mediated activation of IL\u201036 and other IL\u20101 family cytokines in inflammatory conditions, such as psoriasis.<\/jats:p>","DOI":"10.1002\/2211-5463.12406","type":"journal-article","created":{"date-parts":[[2018,2,23]],"date-time":"2018-02-23T20:10:51Z","timestamp":1519416651000},"page":"751-763","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Identification of small\u2010molecule elastase inhibitors as antagonists of IL\u201036 cytokine activation"],"prefix":"10.1002","volume":"8","author":[{"given":"Graeme P.","family":"Sullivan","sequence":"first","affiliation":[{"name":"Molecular Cell Biology Laboratory Department of Genetics The Smurfit Institute Trinity College Dublin 2 Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavel 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