{"id":906,"date":"2014-12-01T13:31:28","date_gmt":"2014-12-01T04:31:28","guid":{"rendered":"http:\/\/misterx95.myds.me\/?p=906"},"modified":"2014-12-01T13:31:28","modified_gmt":"2014-12-01T04:31:28","slug":"journal-club-2014-12-01","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=906","title":{"rendered":"journal club 2014.12.01"},"content":{"rendered":"<h1 id=\"tit0005\" class=\"svTitle\">Antipruritic mechanisms of topical E6005, a phosphodiesterase 4 inhibitor: Inhibition of responses to proteinase-activated receptor 2 stimulation mediated by increase in intracellular cyclic AMP<\/h1>\n<ul class=\"authorGroup noCollab\">\n<li class=\"smh5\"><a id=\"authname_N385f0660N384e2c18\" class=\"authorName\" href=\"http:\/\/www.sciencedirect.com\/science\/article\/pii\/S0923181114002497#\"><span style=\"color: #0066cc\">Tsugunobu Andoh<\/span><\/a>,<\/li>\n<li class=\"smh5\"><a id=\"authname_N385f0660N384e2c54\" class=\"authorName\" href=\"http:\/\/www.sciencedirect.com\/science\/article\/pii\/S0923181114002497#\"><span style=\"color: #0066cc\">Yasushi Kuraishi<\/span><\/a><a id=\"bcor0005\" class=\"intra_ref auth_corr\" title=\"Corresponding author contact information\" href=\"http:\/\/www.sciencedirect.com\/science\/article\/pii\/S0923181114002497#cor0005\"><\/a><sup><span style=\"font-size: small\">, <\/span><\/sup><\/li>\n<\/ul>\n<h2 id=\"authorabs00101\" class=\"secHeading\">Abstract<\/h2>\n<h4 id=\"absSec_1\">Background<\/h4>\n<p id=\"spar0010\">Phosphodiesterase 4 (PDE4), which catalyses the conversion of cyclic adenosine 3\u2032,5\u2032-monophosphate (cAMP) to 5\u2032-AMP, plays a critical role in the pathogenesis of inflammatory disorders. Pruritus is the main symptom of dermatitides, such as atopic dermatitis, and is very difficult to control. Recent studies have shown that the activation of proteinase-activated receptor 2 (PAR<sub><span style=\"font-size: small\">2<\/span><\/sub>) is involved in pruritus in dermatoses in humans and rodents.<\/p>\n<h4 id=\"absSec_2\">Objective<\/h4>\n<p id=\"spar0015\">To investigate the inhibitory effect of E6005, a topically effective PDE4 inhibitor, on PAR<sub><span style=\"font-size: small\">2<\/span><\/sub>-associated itching in mice.<\/p>\n<h4 id=\"absSec_3\">Methods<\/h4>\n<p id=\"spar0020\">Mice were given an intradermal injection of SLIGRL-NH<sub><span style=\"font-size: small\">2<\/span><\/sub> (100\u00a0nmol\/site), a PAR<sub><span style=\"font-size: small\">2<\/span><\/sub> agonist peptide, into the rostral part of the back. E6005 and 8-bromo-cAMP were applied topically and injected intradermally, respectively, to the same site. Scratching bouts were observed as an itch-related behavior, and firing activity of the cutaneous nerve was electrophysiologically recorded. Keratinocytes were isolated from the skin of neonatal mice and cultured for in vitro experiments. The concentrations of cAMP and leukotriene B<sub><span style=\"font-size: small\">4<\/span><\/sub> (LTB<sub><span style=\"font-size: small\">4<\/span><\/sub>) were measured by enzyme immunoassay. The distribution of PDE4 subtypes in the skin was investigated by immunostaining.<\/p>\n<h4 id=\"absSec_4\">Results<\/h4>\n<p id=\"spar0025\">Topical E6005 and intradermal 8-bromo-cAMP significantly inhibited SLIGRL-NH<sub><span style=\"font-size: small\">2<\/span><\/sub>-induced scratching and cutaneous nerve firing. Topical E6005 increased cutaneous cAMP content. Topical E6005 and intradermal 8-bromo-cAMP inhibited cutaneous LTB<sub><span style=\"font-size: small\">4<\/span><\/sub> production induced by SLIGRL-NH<sub><span style=\"font-size: small\">2<\/span><\/sub>, which has been shown to elicit LTB<sub><span style=\"font-size: small\">4<\/span><\/sub>-mediated scratching. E6005 and 8-bromo-cAMP inhibited SLIGRL-NH<sub><span style=\"font-size: small\">2<\/span><\/sub>-induced LTB<sub><span style=\"font-size: small\">4<\/span><\/sub> production in the cultured murine keratinocytes also. PDE4 subtypes were mainly expressed in keratinocytes and mast cells in the skin.<\/p>\n<h4 id=\"absSec_5\">Conclusions<\/h4>\n<p id=\"spar0030\">The results suggest that topical E6005 treatment inhibits PAR<sub><span style=\"font-size: small\">2<\/span><\/sub>-associated itching. Inhibition of LTB<sub><span style=\"font-size: small\">4<\/span><\/sub> production mediated by an increase in cAMP may be partly involved in the antipruritic action of E6005.<\/p>\n<p><!--VALIDHTML--><\/p>\n<div id=\"SD_BA1P\" class=\"sgfNoTitleBar sgfNoGadgetBorder svDoNotLink ui-sortable\"><\/div>\n<p><!--VALIDHTML--><\/p>\n<h2 id=\"kwd_1\" class=\"svKeywords\">Abbreviations<\/h2>\n<ul>\n<li id=\"kw0005\" class=\"svKeywords\">cAMP, cyclic adenosine 3\u2032,5\u2032-monophosphate;<\/li>\n<li id=\"kw0015\" class=\"svKeywords\">EIA, enzyme immunoassay;<\/li>\n<li id=\"kw0025\" class=\"svKeywords\">IgG, immunoglobulin G;<\/li>\n<li id=\"kw0035\" class=\"svKeywords\">LTB<span style=\"font-size: small\"><sub>4<\/sub><\/span>, leukotriene B4;<\/li>\n<li id=\"kw0045\" class=\"svKeywords\">PDE, phosphodiesterase;<\/li>\n<li id=\"kw0055\" class=\"svKeywords\">PAR<span style=\"font-size: small\"><sub>2<\/sub><\/span>, proteinase-activated receptor 2;<\/li>\n<li id=\"kw0065\" class=\"svKeywords\">PBS, phosphate-buffered saline<\/li>\n<\/ul>\n<p class=\"svKeywords\"><a href=\"http:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2014\/12\/dec-presentation.pdf\">dec presentation<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Antipruritic mechanisms of topical E6005, a phosphodiesterase 4 inhibitor: Inhibition of responses to proteinase-activated receptor 2 stimulation mediated by increase in intracellular cyclic AMP Tsugunobu Andoh, Yasushi Kuraishi, Abstract Background Phosphodiesterase 4 (PDE4), which catalyses the conversion of cyclic adenosine 3\u2032,5\u2032-monophosphate (cAMP) to 5\u2032-AMP, plays a critical role in the pathogenesis of inflammatory disorders. Pruritus [&hellip;]<\/p>\n","protected":false},"author":6,"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\/906"}],"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\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=906"}],"version-history":[{"count":1,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/906\/revisions"}],"predecessor-version":[{"id":908,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/906\/revisions\/908"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=906"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=906"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=906"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}