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dc.contributor.authorTumpara, Srinu
dc.contributor.authorLiu, Bin
dc.contributor.authorKorenbaum, Elena
dc.contributor.authorJonigk, Danny
dc.contributor.authorJugert, Frank
dc.contributor.authorWelte, Tobias
dc.contributor.authorJanciauskiene, Sabina
dc.contributor.authorMartinez-Delgado, Beatriz 
dc.contributor.authorGomez-Mariano, Gema Maria 
dc.contributor.authorDeLuca, David S.es_ES
dc.contributor.authorWurm, Florian M.es_ES
dc.contributor.authorWurm, Maria J.es_ES
dc.identifier.citationFront Pharmacol . 2020 Jul 3;11:983es_ES
dc.description.abstractHuman α1-antitrypsin (AAT) is an abundant acute phase glycoprotein expressing anti-protease and immunomodulatory activities, and is used as a biopharmaceutical to treat patients with inherited AAT deficiency. The pleiotropic properties of AAT provide a rationale for using this therapy outside of inherited AAT deficiency. Therapy with AAT is administrated intravenously, yet the alternative routes are being considered. To examine the putative transepidermal application of AAT we used epiCS®, the 3D human epidermis equivalents reconstructed from human primary epidermal keratinocytes. We topically applied various concentrations of AAT protein with a constant volume of 50 µl, prepared in Hank's balance solution, HBSS, to epiCS cultured under bas\al condition or when culture medium supplemented with 100 µg/ml of a combined bacterial lipopolysaccharide (LPS) and peptidoglycan (PGN) mixture. AAT freely diffused across epidermis layers in a concentration and time-dependent manner. Within 18 h topically provided 0.2 mg AAT penetrated well the stratum corneum and localizes within the keratinocytes. The treatments with AAT did not induce obvious morphological changes and damages in keratinocyte layers. As expected, LPS/PGN triggered a strong pro-inflammatory activation of epiCS. AAT exhibited a limited capacity to neutralize the effect of LPS/PGN, but more importantly, it lowered expression of IL-18 and IL-8, and preserved levels of filaggrin, a key protein for maintaining the epidermal barrier integrity. Our findings suggest that the transepidermal route for delivering AAT is worthwhile to explore further. If successful, this approach may offer an easy-to-use therapy with AAT for skin inflammatory diseases.es_ES
dc.description.sponsorshipThis study was supported partly by research funds from ExcellGene SA and by the National Science Center, Poland (grant 2015/17/B/NZ5/01370) and ALTA award for ST (fond number: 19400569).es_ES
dc.publisherFrontiers Media es_ES
dc.subject.meshRNA-Seq-RNA sequencinges_ES
dc.subject.meshInflammation Immunomodulationes_ES
dc.subject.meshEpidermis es_ES
dc.subject.meshtopical-Skin creames_ES
dc.titleThe Delivery of α1-Antitrypsin Therapy Through Transepidermal Route: Worthwhile to Explore.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderNational Science Centre (Polonia) 
dc.identifier.journalFrontiers in pharmacologyes_ES
dc.repisalud.centroISCIII::Instituto de Investigación de Enfermedades Rarases_ES
dc.rights.accessRightsopen accesses_ES

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