{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:30:49Z","timestamp":1790886649094,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T00:00:00Z","timestamp":1585612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE), which is a chronic autoimmune disease. However, the detailed mechanisms underlying this disorder have remained unclear. Alpha2\u2010antiplasmin (\u03b12AP) is known to perform various functions, such as plasmin inhibition and cytokine production, and to be associated with immune and inflammatory responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the roles of \u03b12AP in the pathogenesis of LN using a pristane\u2010induced lupus mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The levels of plasmin\u2010\u03b12AP complex and \u03b12AP were elevated in the lupus model mice. In addition, \u03b12AP deficiency attenuated the pristane\u2010induced glomerular cell proliferation, mesangial matrix expansion, collagen production, fibrin deposition, immunoglobulin G deposition, and proinflammatory cytokine production in the model mice. We also showed that interferon\u2010\u03b3 (IFN\u2010\u03b3), which is an essential inducer of LN, induced \u03b12AP production through the c\u2010Jun N\u2010terminal kinase (JNK) pathway in fibroblasts. In addition, plasmin attenuated the IFN\u2010\u03b3\u2010induced proinflammatory cytokine production through the AMPK pathway in macrophages, and \u03b12AP eliminated these effects. Furthermore, we showed that \u03b12AP induced proinflammatory cytokine production through the ERK1\/2 and JNK pathways in macrophages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>\u03b12AP regulates the inflammatory responses through plasmin inhibition and proinflammatory cytokine production and is associated with the development of LN. Our findings may be used to develop a novel therapeutic approach for SLE.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.302","type":"journal-article","created":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T05:52:10Z","timestamp":1585720330000},"page":"267-278","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["\u03b12AP is associated with the development of lupus nephritis through the regulation of plasmin inhibition and inflammatory responses"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9741-2113","authenticated-orcid":false,"given":"Yosuke","family":"Kanno","sequence":"first","affiliation":[{"name":"Department of Clinical Pathological Biochemistry, Faculty of Pharmaceutical Science Doshisha Women's College of Liberal Arts Kyoto Japan"},{"name":"Department of Dermatology Gifu University Graduate School of Medicine Gifu 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