{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T09:20:48Z","timestamp":1789809648219,"version":"4.0.1"},"reference-count":51,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T00:00:00Z","timestamp":1540166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"International Pemphigus and Pemphigoid Foundation"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"Abstract<\/jats:title>\n \n Cutaneous deposition of eosinophil degranulation proteins is a major feature of eosinophil\u2010rich cutaneous diseases including bullous pemphigoid (\n BP<\/jats:styled-content>\n ). We sought to better understand the effect of two of these proteins \u2013 eosinophil cationic protein (\n ECP<\/jats:styled-content>\n ) and eosinophil\u2010derived neurotoxin (\n EDN<\/jats:styled-content>\n ), on human keratinocytes using the Het\u20101A cell line. To evaluate expression of key cytokines and chemokines observed in\n BP<\/jats:styled-content>\n as well as metal metalloprotease 9 (\n MMP<\/jats:styled-content>\n 9), we performed\n qPCR<\/jats:styled-content>\n and in\u2010cell Western assays on cells treated with either\n ECP<\/jats:styled-content>\n or\n EDN<\/jats:styled-content>\n . We further evaluated the effect of\n ECP<\/jats:styled-content>\n and\n EDN<\/jats:styled-content>\n on keratinocyte survival, generation of reactive oxygen species (\n ROS<\/jats:styled-content>\n ) and apoptosis. Lastly, we assessed\n ECP<\/jats:styled-content>\n and\n EDN<\/jats:styled-content>\n 's ability to induce keratinocyte detachment from provisional matrix. Treatment of keratinocytes with\n ECP<\/jats:styled-content>\n and\n EDN<\/jats:styled-content>\n resulted in significant increases in\n IL<\/jats:styled-content>\n \u20105, eotaxin\u20101 and\n CCL<\/jats:styled-content>\n 5 (\n RANTES<\/jats:styled-content>\n ) expression at both\n mRNA<\/jats:styled-content>\n and protein levels, but not\n IL<\/jats:styled-content>\n \u201017 or\n IL<\/jats:styled-content>\n \u201031.\n ECP<\/jats:styled-content>\n and\n EDN<\/jats:styled-content>\n also upregulate\n MMP<\/jats:styled-content>\n 9 production. Inhibiting\n MMP<\/jats:styled-content>\n 9, we confirmed that keratinocyte expression of\n IL<\/jats:styled-content>\n \u20105, eotaxin\u20101 and\n RANTES<\/jats:styled-content>\n was independent from\n MMP<\/jats:styled-content>\n 9. Both\n ECP<\/jats:styled-content>\n and\n EDN<\/jats:styled-content>\n were cytotoxic to keratinocytes, inducing\n ROS<\/jats:styled-content>\n formation and apoptosis through a mitochondrion\u2010dependent pathway as evidenced by results of terminal deoxynucleotidyl transferase\n dUTP<\/jats:styled-content>\n nick\u2010end labelling (\n TUNEL<\/jats:styled-content>\n ) and cytochrome c release assays, respectively.\n ECP<\/jats:styled-content>\n but not\n EDN<\/jats:styled-content>\n led to significant keratinocyte detachment from provisional matrix. These findings demonstrate that the pathogenic effects of\n ECP<\/jats:styled-content>\n and\n EDN<\/jats:styled-content>\n in\n BP<\/jats:styled-content>\n may result from their direct action on keratinocytes, and as such may became a target for future therapies in eosinophil\u2010rich cutaneous diseases.\n <\/jats:p>","DOI":"10.1111\/exd.13782","type":"journal-article","created":{"date-parts":[[2018,9,16]],"date-time":"2018-09-16T09:16:53Z","timestamp":1537089413000},"page":"1322-1327","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Mechanisms of pathogenic effects of eosinophil cationic protein and eosinophil\u2010derived neurotoxin on human keratinocytes"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2906-2454","authenticated-orcid":false,"given":"Kyle T.","family":"Amber","sequence":"first","affiliation":[{"name":"Department of Dermatology University of California Irvine Irvine California"},{"name":"Department of Dermatology University of Illinois at Chicago Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Chernyavsky","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of California Irvine Irvine California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna F.","family":"Agnoletti","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of California Irvine Irvine California"},{"name":"DISSAL Section of Dermatology San Martino Policlinic Hospital Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Cozzani","sequence":"additional","affiliation":[{"name":"DISSAL Section of Dermatology San Martino Policlinic Hospital Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei A.","family":"Grando","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of California Irvine Irvine California"},{"name":"Institute for Immunology and Departments of Dermatology and Biological Chemistry University of California Irvine California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2018.00201"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-015-8485-8"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R113.546218"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.3MR1217-476R"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-005-4777-2"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2007.00650.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M803516200"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1515\/bc.2011.037"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057318"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/321613a0"},{"key":"e_1_2_8_12_1","first-page":"593","volume":"38","author":"Trocme S. 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