Optical control of adenosine A3 receptor function in psoriasis
López-Cano, Marc (Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental)
Filgaira, Ingrid (Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental)
Nolen, Ernest G. (Colgate University)
Cabré Segura, Gisela (Universitat Autònoma de Barcelona. Departament de Química)
Hernando Campos, Jordi (Universitat Autònoma de Barcelona. Departament de Química)
Tosh, Dilip K. (National Institutes of Health. National Institute of Diabetes and Digestive and Kidney Diseases (USA))
Jacobson, Kenneth A. (National Institutes of Health. National Institute of Diabetes and Digestive and Kidney Diseases (USA))
Soler, Concepció (Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental)
Ciruela, Francisco (Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental)

Date:	2021
Abstract:	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.
Grants:	Agencia Estatal de Investigación SAF2017-87349-R Agencia Estatal de Investigación SAF2017-83815-R Ministerio de Economía y Competitividad PIE14/00034 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1604
Note:	Altres ajuts: CERCA Programme/Generalitat de Catalunya i Fundació la Marató de TV3 (Grant 20152031)
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	Psoriasis ; Anti-inflammatory ; Adenosine receptor ; Photopharmacology
Published in:	Pharmacological Research, Vol. 170 (August 2021) , art. 105731, ISSN 1096-1186

DOI: 10.1016/j.phrs.2021.105731
PMID: 34157422

Postprint 17 p, 1000.6 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Experimental sciences > Group in Electrochemistry, Photochemistry and Organic Reactivity (GEFRO)
Articles > Research articles
Articles > Published articles