Optical control of adenosine A3 receptor function in psoriasis

Psoriasis is a chronic and relapsing inflammatory skin disease lacking a cure that affects approximately 2% of the population. Defective keratinocyte proliferation and differentiation, and aberrant immune responses are major factors in its pathogenesis. Available treatments for moderate to severe ps...

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Autores: López Cano, Marc|||0000-0001-8885-3726, Filgaira, Ingrid|||0000-0002-9886-3925, Nolen, Ernest G., Cabré Segura, Gisela|||0000-0003-3104-3364, Hernando, Jordi|||0000-0002-1126-4138, Tosh, Dilip K., Jacobson, Kenneth A.|||0000-0001-8104-1493, Soler, Concepció|||0000-0001-6502-5012, Ciruela, Francisco|||0000-0003-0832-3739
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:266060
Acceso en línea:https://ddd.uab.cat/record/266060
https://dx.doi.org/urn:doi:10.1016/j.phrs.2021.105731
Access Level:acceso abierto
Palabra clave:Psoriasis
Anti-inflammatory
Adenosine receptor
Photopharmacology
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spelling Optical control of adenosine A3 receptor function in psoriasisLópez Cano, Marc|||0000-0001-8885-3726Filgaira, Ingrid|||0000-0002-9886-3925Nolen, Ernest G.Cabré Segura, Gisela|||0000-0003-3104-3364Hernando, Jordi|||0000-0002-1126-4138Tosh, Dilip K.Jacobson, Kenneth A.|||0000-0001-8104-1493Soler, Concepció|||0000-0001-6502-5012Ciruela, Francisco|||0000-0003-0832-3739PsoriasisAnti-inflammatoryAdenosine receptorPhotopharmacologyPsoriasis is a chronic and relapsing inflammatory skin disease lacking a cure that affects approximately 2% of the population. Defective keratinocyte proliferation and differentiation, and aberrant immune responses are major factors in its pathogenesis. Available treatments for moderate to severe psoriasis are directed to immune system causing systemic immunosuppression over time, and thus concomitant serious side effects (i.e. infections and cancer) may appear. In recent years, the G protein-coupled A receptor (AR) for adenosine has been suggested as a novel and very promising therapeutic target for psoriasis. Accordingly, selective, and high affinity AR agonists are known to induce robust anti-inflammatory effects in animal models of autoimmune inflammatory diseases. Here, we demonstrated the efficacy of a selective AR agonist, namely MRS5698, in preventing the psoriatic-like phenotype in the IL-23 mouse model of psoriasis. Subsequently, we photocaged this molecule with a coumarin moiety to yield the first photosensitive AR agonist, MRS7344, which in photopharmacological experiments prevented the psoriatic-like phenotype in the IL-23 animal model. Thus, we have demonstrated the feasibility of using a non-invasive, site-specific, light-directed approach to psoriasis treatment. 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/266060https://dx.doi.org/urn:doi:10.1016/j.phrs.2021.105731reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 SAF2017-87349-RAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 SAF2017-83815-RMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 PIE14/00034Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-1604open accesshttp://purl.org/coar/access_right/c_abf2Aquesta url de drets no existeix a la base de dades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2660602026-06-06T12:50:31Z
dc.title.none.fl_str_mv Optical control of adenosine A3 receptor function in psoriasis
title Optical control of adenosine A3 receptor function in psoriasis
spellingShingle Optical control of adenosine A3 receptor function in psoriasis
López Cano, Marc|||0000-0001-8885-3726
Psoriasis
Anti-inflammatory
Adenosine receptor
Photopharmacology
title_short Optical control of adenosine A3 receptor function in psoriasis
title_full Optical control of adenosine A3 receptor function in psoriasis
title_fullStr Optical control of adenosine A3 receptor function in psoriasis
title_full_unstemmed Optical control of adenosine A3 receptor function in psoriasis
title_sort Optical control of adenosine A3 receptor function in psoriasis
dc.creator.none.fl_str_mv López Cano, Marc|||0000-0001-8885-3726
Filgaira, Ingrid|||0000-0002-9886-3925
Nolen, Ernest G.
Cabré Segura, Gisela|||0000-0003-3104-3364
Hernando, Jordi|||0000-0002-1126-4138
Tosh, Dilip K.
Jacobson, Kenneth A.|||0000-0001-8104-1493
Soler, Concepció|||0000-0001-6502-5012
Ciruela, Francisco|||0000-0003-0832-3739
author López Cano, Marc|||0000-0001-8885-3726
author_facet López Cano, Marc|||0000-0001-8885-3726
Filgaira, Ingrid|||0000-0002-9886-3925
Nolen, Ernest G.
Cabré Segura, Gisela|||0000-0003-3104-3364
Hernando, Jordi|||0000-0002-1126-4138
Tosh, Dilip K.
Jacobson, Kenneth A.|||0000-0001-8104-1493
Soler, Concepció|||0000-0001-6502-5012
Ciruela, Francisco|||0000-0003-0832-3739
author_role author
author2 Filgaira, Ingrid|||0000-0002-9886-3925
Nolen, Ernest G.
Cabré Segura, Gisela|||0000-0003-3104-3364
Hernando, Jordi|||0000-0002-1126-4138
Tosh, Dilip K.
Jacobson, Kenneth A.|||0000-0001-8104-1493
Soler, Concepció|||0000-0001-6502-5012
Ciruela, Francisco|||0000-0003-0832-3739
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Psoriasis
Anti-inflammatory
Adenosine receptor
Photopharmacology
topic Psoriasis
Anti-inflammatory
Adenosine receptor
Photopharmacology
description Psoriasis is a chronic and relapsing inflammatory skin disease lacking a cure that affects approximately 2% of the population. Defective keratinocyte proliferation and differentiation, and aberrant immune responses are major factors in its pathogenesis. Available treatments for moderate to severe psoriasis are directed to immune system causing systemic immunosuppression over time, and thus concomitant serious side effects (i.e. infections and cancer) may appear. In recent years, the G protein-coupled A receptor (AR) for adenosine has been suggested as a novel and very promising therapeutic target for psoriasis. Accordingly, selective, and high affinity AR agonists are known to induce robust anti-inflammatory effects in animal models of autoimmune inflammatory diseases. Here, we demonstrated the efficacy of a selective AR agonist, namely MRS5698, in preventing the psoriatic-like phenotype in the IL-23 mouse model of psoriasis. Subsequently, we photocaged this molecule with a coumarin moiety to yield the first photosensitive AR agonist, MRS7344, which in photopharmacological experiments prevented the psoriatic-like phenotype in the IL-23 animal model. Thus, we have demonstrated the feasibility of using a non-invasive, site-specific, light-directed approach to psoriasis treatment.
publishDate 2021
dc.date.none.fl_str_mv 2
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/266060
https://dx.doi.org/urn:doi:10.1016/j.phrs.2021.105731
url https://ddd.uab.cat/record/266060
https://dx.doi.org/urn:doi:10.1016/j.phrs.2021.105731
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 SAF2017-87349-R
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 SAF2017-83815-R
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PIE14/00034
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-1604
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Aquesta url de drets no existeix a la base de dades.
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
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Aquesta url de drets no existeix a la base de dades.
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
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collection Dipòsit Digital de Documents de la UAB
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