<> <http://www.w3.org/2000/01/rdf-schema#comment> "The repository administrator has not yet configured an RDF license."^^<http://www.w3.org/2001/XMLSchema#string> .
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<https://discovery.ucl.ac.uk/id/eprint/1543766> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/Article> .
<https://discovery.ucl.ac.uk/id/eprint/1543766> <http://purl.org/dc/terms/title> "Persistent kallikrein5 activation induces atopic dermatitis-like skin architecture independent of PAR2 activity."^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/1543766> <http://purl.org/ontology/bibo/abstract> "BACKGROUND: Up-regulation of kallikreins (KLK) including KLK5 has been reported in atopic dermatitis (AD). KLK5 has biological functions which include degrading desmosomal proteins and inducing pro-inflammatory cytokine secretion through protease activated receptor 2 (PAR2). However, due to the complex interactions between various cells in AD inflamed skin, it is difficult to dissect the precise and multiple roles of up-regulated KLK5 in AD skin. OBJECTIVE: We investigated the effect of up-regulated KLK5 on the expression of epidermal related proteins and cytokines in keratinocytes and on skin architecture. METHODS: Lesional and non-lesional AD skin biopsies were collected for analysis of morphology and protein expression. The relationship between KLK5 and barrier related molecules was investigated using an ex-vivo dermatitis skin model with transient KLK5 expression and a cell model with persistent KLK5 expression. The influence of up-regulated KLK5 on epidermal morphology was investigated using an in vivo skin graft model. RESULTS: Up-regulation of KLK5 and abnormal expression of desmoglein 1 (DSG1) and filaggrin (FLG), but not PAR2 were identified in AD skin. PAR2 was increased in response to transient up-regulation of KLK5, while persistently up-regulated KLK5 did not show this effect. Persistently up-regulated KLK5 degraded DSG1 and stimulated secretion of IL-8, IL-10 and TSLP independent of PAR2 activity. With control of higher KLK5 activity by the inhibitor SFTI-G, restoration of DSG1 expression and a reduction in AD-related cytokine IL-8, TLSP and IL-10 secretion were observed. Furthermore, persistently elevated KLK5 could induce AD-like skin architecture in an in vivo skin graft model. . CONCLUSION: Persistently up-regulated KLK5 resulted in AD-like skin architecture and secretion of AD-related cytokines from keratinocytes in a PAR-2 independent manner. Inhibition of KLK5-mediated effects may offer potential as a therapeutic approach in AD."^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/1543766> <http://purl.org/dc/terms/date> "2017-11" .
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<https://discovery.ucl.ac.uk/id/eprint/1543766> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-1ceac8950f2d4e0e18c9053e09c3eb8c> .
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<https://discovery.ucl.ac.uk/id/eprint/1543766> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-c0eaab8934a690316bd3131a2db2df4e> .
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<https://discovery.ucl.ac.uk/id/person/ext-c0eaab8934a690316bd3131a2db2df4e> <http://xmlns.com/foaf/0.1/familyName> "Di"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-c0eaab8934a690316bd3131a2db2df4e> <http://xmlns.com/foaf/0.1/name> "WL Di"^^<http://www.w3.org/2001/XMLSchema#string> .
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<https://discovery.ucl.ac.uk/id/person/ext-ecfba5bc563b4fba8e9350c68c12984b> <http://xmlns.com/foaf/0.1/givenName> "PS"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-ecfba5bc563b4fba8e9350c68c12984b> <http://xmlns.com/foaf/0.1/familyName> "Friedmann"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-ecfba5bc563b4fba8e9350c68c12984b> <http://xmlns.com/foaf/0.1/name> "PS Friedmann"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-d0dd0aabdefd74ad647bb2f9d48c9d8b> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> .
<https://discovery.ucl.ac.uk/id/person/ext-d0dd0aabdefd74ad647bb2f9d48c9d8b> <http://xmlns.com/foaf/0.1/givenName> "C"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-d0dd0aabdefd74ad647bb2f9d48c9d8b> <http://xmlns.com/foaf/0.1/familyName> "Pickard"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-d0dd0aabdefd74ad647bb2f9d48c9d8b> <http://xmlns.com/foaf/0.1/name> "C Pickard"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-52faadd2a38f4069dfe8d24bf745ce74> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> .
<https://discovery.ucl.ac.uk/id/person/ext-52faadd2a38f4069dfe8d24bf745ce74> <http://xmlns.com/foaf/0.1/givenName> "JI"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-52faadd2a38f4069dfe8d24bf745ce74> <http://xmlns.com/foaf/0.1/familyName> "Harper"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-52faadd2a38f4069dfe8d24bf745ce74> <http://xmlns.com/foaf/0.1/name> "JI Harper"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-bc5623c4e86eea03a7af3753d245cd92> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> .
<https://discovery.ucl.ac.uk/id/person/ext-bc5623c4e86eea03a7af3753d245cd92> <http://xmlns.com/foaf/0.1/givenName> "Y"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-bc5623c4e86eea03a7af3753d245cd92> <http://xmlns.com/foaf/0.1/familyName> "Zhu"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-bc5623c4e86eea03a7af3753d245cd92> <http://xmlns.com/foaf/0.1/name> "Y Zhu"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-e90ee93459edad8021f28cd25fcd7ab7> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> .
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<https://discovery.ucl.ac.uk/id/person/ext-e90ee93459edad8021f28cd25fcd7ab7> <http://xmlns.com/foaf/0.1/familyName> "Underwood"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/person/ext-e90ee93459edad8021f28cd25fcd7ab7> <http://xmlns.com/foaf/0.1/name> "J Underwood"^^<http://www.w3.org/2001/XMLSchema#string> .
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