{"id":3550,"date":"2025-10-27T10:21:05","date_gmt":"2025-10-27T01:21:05","guid":{"rendered":"https:\/\/misterx95.myds.me\/wordpress\/?p=3550"},"modified":"2025-10-28T05:56:03","modified_gmt":"2025-10-27T20:56:03","slug":"topical-application-of-a-pde4-inhibitorameliorates-atopic-dermatitis-throughinhibition-of-basophil-il-4-production","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=3550","title":{"rendered":"Journal Club 2025.10.27"},"content":{"rendered":"\n<p>gyemin noh <\/p>\n\n\n\n<h2>Topical Application of a PDE4 InhibitorAmeliorates Atopic Dermatitis throughInhibition of Basophil IL-4 Production<\/h2>\n\n\n\n<h4>Abstract<\/h4>\n\n\n\n<p>Phosphodiesterase 4 inhibitors have been approved for the treatment of atopic dermatitis. However, the<br>cellular and molecular mechanisms underlying their therapeutic effect remain to be fully elucidated. In this<br>study, we addressed this unsolved issue by analyzing the action of difamilast, a novel phosphodiesterase 4<br>inhibitor, on an oxazolone-induced skin allergic inflammation commonly used as a mouse model of atopic<br>dermatitis. Topical application of difamilast ameliorated skin inflammation in association with reduced IL-4<br>expression even when the treatment commenced 4 days after the initiation of oxazolone challenge, showing<br>its therapeutic effect on atopic dermatitis. IL-4edeficient mice displayed milder skin inflammation than did<br>wild-type mice, and the difamilast treatment had little or no further therapeutic effect. This was also the case in<br>mice depleted of basophils, predominant producers of IL-4 in the skin lesion, suggesting that difamilast may act<br>on basophils. Notably, basophils accumulating in the skin lesion showed highly upregulated expression of<br>Pde4b encoding the B subtype of the phosphodiesterase 4 family. Difamilast suppressed IL-4 production from<br>basophils activated in vitro, at least in part, through inhibition of ERK phosphorylation. Taken together, difamilast appeared to ameliorate atopic dermatitis inflammation through the suppression of basophil IL-4 production in the skin lesion.<\/p>\n\n\n\n<p><br>Keywords: Allergic inflammation, Difamilast, ERK, Mouse model, PDE4B<\/p>\n\n\n\n<div class=\"wp-block-file\"><object class=\"wp-block-file__embed\" data=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2025\/10\/1-s2.0-S0022202X23029202-main.pdf\" type=\"application\/pdf\" style=\"width:100%;height:610px\" aria-label=\"Embed of 1-s2.0-S0022202X23029202-main.\"><\/object><a id=\"wp-block-file--media-5c4db658-c6dd-436d-9417-6da0b6be0d63\" href=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2025\/10\/1-s2.0-S0022202X23029202-main.pdf\">1-s2.0-S0022202X23029202-main<\/a><a href=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2025\/10\/1-s2.0-S0022202X23029202-main.pdf\" class=\"wp-block-file__button wp-element-button\" download aria-describedby=\"wp-block-file--media-5c4db658-c6dd-436d-9417-6da0b6be0d63\">Download<\/a><\/div>\n","protected":false},"excerpt":{"rendered":"<p>gyemin noh Topical Application of a PDE4 InhibitorAmeliorates Atopic Dermatitis throughInhibition of Basophil IL-4 Production Abstract Phosphodiesterase 4 inhibitors have been approved for the treatment of atopic dermatitis. However, thecellular and molecular mechanisms underlying their therapeutic effect remain to be fully elucidated. In thisstudy, we addressed this unsolved issue by analyzing the action of difamilast, [&hellip;]<\/p>\n","protected":false},"author":23,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}}},"categories":[1],"tags":[],"_links":{"self":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/3550"}],"collection":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/users\/23"}],"replies":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=3550"}],"version-history":[{"count":4,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/3550\/revisions"}],"predecessor-version":[{"id":3556,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/3550\/revisions\/3556"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=3550"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=3550"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=3550"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}