{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T20:16:32Z","timestamp":1777148192178,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,6,28]],"date-time":"2018-06-28T00:00:00Z","timestamp":1530144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["Kakenhi Grant Number JP16K10128"],"award-info":[{"award-number":["Kakenhi Grant Number JP16K10128"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Epidermal keratinocytes initiate skin inflammation by activating immune cells. The skin barrier is disrupted in atopic dermatitis (<jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>) and epidermal keratinocytes can be exposed to environmental stimuli, such as house dust mite (<jats:styled-content style=\"fixed-case\">HDM<\/jats:styled-content>) allergens. We showed previously that<jats:styled-content style=\"fixed-case\">HDM<\/jats:styled-content>allergens activate the<jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>3\u00a0inflammasome of keratinocytes, thereby releasing pro\u2010inflammatory cytokines. Heparinoid is an effective moisturizer for atopic dry skin. However, a recent report showed that heparinoid treatment can improve inflammation of lichen planus. Therefore, we hypothesized that it acts on epidermal keratinocytes not only as a moisturizer, but also as a suppressant of the triggers of skin inflammation. We found that<jats:styled-content style=\"fixed-case\">HDM<\/jats:styled-content>allergen\u2010induced interleukin (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>)\u20101\u03b2 release from keratinocytes was inhibited significantly by heparinoid pretreatment without affecting cell viability. However, heparinoid did not affect caspase\u20101 release, suggesting that heparinoid did not affect<jats:styled-content style=\"fixed-case\">HDM<\/jats:styled-content>allergen\u2010induced inflammasome activation. Heparinoid treatment not only decreased intracellular levels of pro\u2010<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2, but also suppressed<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2 messenger<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>(<jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>) expression in keratinocytes. Among the intracellular signalling pathways, the activation of extracellular signal\u2010regulated kinase and p38 pathways, which are required for<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2 expression in keratinocytes, was inhibited by heparinoid treatment. The inhibitory effect of heparinoid on<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2<jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>expression was also confirmed with living skin equivalents. Our results demonstrated that heparinoid suppresses the initiation of keratinocyte\u2010mediated skin inflammation.<\/jats:p>","DOI":"10.1111\/exd.13685","type":"journal-article","created":{"date-parts":[[2018,5,13]],"date-time":"2018-05-13T18:43:58Z","timestamp":1526237038000},"page":"981-988","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Heparinoid suppresses Der p\u2010induced<scp>IL<\/scp>\u20101\u03b2 production by inhibiting<scp>ERK<\/scp>and p38<scp>MAPK<\/scp>pathways in keratinocytes"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7257-5784","authenticated-orcid":false,"given":"Ryo","family":"Utsunomiya","sequence":"first","affiliation":[{"name":"Department of Dermatology Ehime University Graduate School of Medicine Toon City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1487-7466","authenticated-orcid":false,"given":"Xiuju","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Dermatology Ehime University Graduate School of Medicine Toon City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masamoto","family":"Murakami","sequence":"additional","affiliation":[{"name":"Department of Dermatology Ehime University Graduate School of Medicine Toon City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kana","family":"Masuda","sequence":"additional","affiliation":[{"name":"Department of Dermatology Ehime University Graduate School of Medicine Toon City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidenori","family":"Okazaki","sequence":"additional","affiliation":[{"name":"Department of Dermatology Ehime Prefectural Central Hospital Matsuyama City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teruko","family":"Tsuda","sequence":"additional","affiliation":[{"name":"Department of Dermatology Ehime University Graduate School of Medicine Toon City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Dermatology Ehime University Graduate School of Medicine Toon City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Shiraishi","sequence":"additional","affiliation":[{"name":"Department of Dermatology Ehime University Graduate School of Medicine Toon City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikiko","family":"Tohyama","sequence":"additional","affiliation":[{"name":"Department of Dermatology Ehime University Graduate School of Medicine Toon City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Sayama","sequence":"additional","affiliation":[{"name":"Department of Dermatology Ehime University Graduate School of Medicine Toon City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,6,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2013.02.001"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.2010.01052.x"},{"key":"e_1_2_8_4_1","first-page":"899","volume":"7","author":"Proksch E.","year":"2009","journal-title":"J. Dtsch. Dermatol. Ges."},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.12.006"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2009.09582.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.13301"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajd.12179"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2014.09.004"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.07.060"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.08.005"},{"key":"e_1_2_8_12_1","first-page":"277","volume-title":"Carbohydrates Drug Design","author":"Linhardt R. J.","year":"1997"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000029916"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2336\/nishinihonhifu.69.44"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0738-081X(02)00373-5"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1296172"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1211\/0022357021778853"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajd.12080"},{"key":"e_1_2_8_19_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.5070\/D32ZH8X3VF","volume":"11","author":"Verg\u00e9s J.","year":"2005","journal-title":"Dermatol. Online J."},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2009.09.009"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2005.07.001"},{"key":"e_1_2_8_22_1","first-page":"469","volume":"19","author":"Cho J.","year":"2007","journal-title":"Int. J. Mol. Med."},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2005.08.019"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxn048"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-1999-13990"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.2.1272"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-011-1146-8"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.13160"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3646"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3150"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067666"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.027375"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2004.02.001"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2015.11.008"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2008.06.008"},{"key":"e_1_2_8_36_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1742-7843.2007.00158.x","volume":"102","author":"Jomphe C.","year":"2007","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1177\/1947601911407323"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1840698"},{"key":"e_1_2_8_39_1","first-page":"218","volume":"28","author":"Cook P. W.","year":"1992","journal-title":"Dev. Biol."},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2015.06.004"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2622"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00401.2005"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21764"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01053"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002001"},{"key":"e_1_2_8_46_1","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1684\/ejd.2013.2169","volume":"23","author":"Luger T.","year":"2013","journal-title":"Eur. J. Dermatol."}],"container-title":["Experimental Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fexd.13685","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/exd.13685","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T18:45:12Z","timestamp":1720291512000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/exd.13685"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,28]]},"references-count":45,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2018,9]]}},"alternative-id":["10.1111\/exd.13685"],"URL":"https:\/\/doi.org\/10.1111\/exd.13685","archive":["Portico"],"relation":{},"ISSN":["0906-6705","1600-0625"],"issn-type":[{"value":"0906-6705","type":"print"},{"value":"1600-0625","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,28]]},"assertion":[{"value":"2018-05-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}