Adenosine A2B receptor agonist improves epidermal barrier integrity in a murine model of epidermal hyperplasia
Adenosine regulates multiple physiological processes through the activation of four receptor subtypes, of which the A2B adenosine receptor (A2BAR) has the lowest affinity for adenosine. Being the adenosine receptor subtype most prominently expressed in epidermis, we recently described the antiprolif...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-04-01
|
| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332224002853 |
| _version_ | 1797248398305263616 |
|---|---|
| author | Asunción Marín-Castejón Miguel Marco-Bonilla M. Carmen Terencio Jorge Arasa M. Carmen Carceller M. Luisa Ferrandiz M. Antonia Noguera Rosa Andrés-Ejarque M. Carmen Montesinos |
| author_facet | Asunción Marín-Castejón Miguel Marco-Bonilla M. Carmen Terencio Jorge Arasa M. Carmen Carceller M. Luisa Ferrandiz M. Antonia Noguera Rosa Andrés-Ejarque M. Carmen Montesinos |
| author_sort | Asunción Marín-Castejón |
| collection | DOAJ |
| description | Adenosine regulates multiple physiological processes through the activation of four receptor subtypes, of which the A2B adenosine receptor (A2BAR) has the lowest affinity for adenosine. Being the adenosine receptor subtype most prominently expressed in epidermis, we recently described the antiproliferative and anti-inflammatory effect of the selective A2BAR agonist BAY60–6583 (BAY) in human keratinocytes stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA), so we sought to establish the effect of topical application of BAY in a model of murine epidermal hyperplasia.Topical application of BAY (1 or 10 μg/site) prevented the inflammatory reaction and skin lesions induced by TPA, minimizing hyperproliferation and acanthosis, as well as the expression of specific markers of proliferative keratinocytes. On the other hand, pre-treatment with the selective A2BAR antagonist, PSB-1115 (PSB, 5 or 50 μg/site) reversed these beneficial effects. Additionally, BAY application normalized the expression of epidermal barrier proteins, whose integrity is altered in inflammatory skin diseases, while treatment with the antagonist alone worsened it.Our results, besides confirming the anti-inflammatory and antiproliferative effects of the A2BAR agonist, further demonstrate a role of A2BAR activation to preserve the epidermal barrier. Therefore, the activation of A2BAR may constitute a possible new pharmacological target for the treatment of skin inflammatory diseases such as psoriasis. |
| first_indexed | 2024-04-24T20:13:57Z |
| format | Article |
| id | doaj.art-2b0a3caaaf1d4b3e8a2fdde569509ea9 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-24T20:13:57Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-2b0a3caaaf1d4b3e8a2fdde569509ea92024-03-23T06:23:01ZengElsevierBiomedicine & Pharmacotherapy0753-33222024-04-01173116401Adenosine A2B receptor agonist improves epidermal barrier integrity in a murine model of epidermal hyperplasiaAsunción Marín-Castejón0Miguel Marco-Bonilla1M. Carmen Terencio2Jorge Arasa3M. Carmen Carceller4M. Luisa Ferrandiz5M. Antonia Noguera6Rosa Andrés-Ejarque7M. Carmen Montesinos8Department of Pharmacology, Faculty of Pharmacy and Food Sciences, University of Valencia, Av. Vicent Andrés Estellés s/n, Burjassot 46100, Valencia, Spain; Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM), University of Valencia, Polytechnic University of Valencia, Av. Vicent A. Estellés s/n, Burjassot 46100, Valencia, SpainDepartment of Pharmacology, Faculty of Pharmacy and Food Sciences, University of Valencia, Av. Vicent Andrés Estellés s/n, Burjassot 46100, Valencia, SpainDepartment of Pharmacology, Faculty of Pharmacy and Food Sciences, University of Valencia, Av. Vicent Andrés Estellés s/n, Burjassot 46100, Valencia, Spain; Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM), University of Valencia, Polytechnic University of Valencia, Av. Vicent A. Estellés s/n, Burjassot 46100, Valencia, SpainDepartment of Pharmacology, Faculty of Pharmacy and Food Sciences, University of Valencia, Av. Vicent Andrés Estellés s/n, Burjassot 46100, Valencia, Spain; Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM), University of Valencia, Polytechnic University of Valencia, Av. Vicent A. Estellés s/n, Burjassot 46100, Valencia, SpainInteruniversity Research Institute for Molecular Recognition and Technological Development (IDM), University of Valencia, Polytechnic University of Valencia, Av. Vicent A. Estellés s/n, Burjassot 46100, Valencia, Spain; Department of Pharmacy, Pharmaceutical Technology and Parasitology, Faculty of Pharmacy and Food Sciences, University of Valencia, Av. Vicent Andrés Estellés s/n, Burjassot 46100, Valencia, SpainDepartment of Pharmacology, Faculty of Pharmacy and Food Sciences, University of Valencia, Av. Vicent Andrés Estellés s/n, Burjassot 46100, Valencia, Spain; Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM), University of Valencia, Polytechnic University of Valencia, Av. Vicent A. Estellés s/n, Burjassot 46100, Valencia, SpainDepartment of Pharmacology, Faculty of Pharmacy and Food Sciences, University of Valencia, Av. Vicent Andrés Estellés s/n, Burjassot 46100, Valencia, Spain; Instituto Universitario de Biotecnología y Biomedicina (BIOTECMED) Universitat de València, Av. Vicent A. Estellés s/n, Burjassot 46100, Valencia, SpainCentre for Inflammation Biology and Cancer Immunology, School of Immunology & Microbial Sciences, King's College London, London SE1 1UL, UKDepartment of Pharmacology, Faculty of Pharmacy and Food Sciences, University of Valencia, Av. Vicent Andrés Estellés s/n, Burjassot 46100, Valencia, Spain; Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM), University of Valencia, Polytechnic University of Valencia, Av. Vicent A. Estellés s/n, Burjassot 46100, Valencia, Spain; Correspondence to: Department of Pharmacology, University of Valencia, Avenida Vicent Andrés Estellés s/n, Spain.Adenosine regulates multiple physiological processes through the activation of four receptor subtypes, of which the A2B adenosine receptor (A2BAR) has the lowest affinity for adenosine. Being the adenosine receptor subtype most prominently expressed in epidermis, we recently described the antiproliferative and anti-inflammatory effect of the selective A2BAR agonist BAY60–6583 (BAY) in human keratinocytes stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA), so we sought to establish the effect of topical application of BAY in a model of murine epidermal hyperplasia.Topical application of BAY (1 or 10 μg/site) prevented the inflammatory reaction and skin lesions induced by TPA, minimizing hyperproliferation and acanthosis, as well as the expression of specific markers of proliferative keratinocytes. On the other hand, pre-treatment with the selective A2BAR antagonist, PSB-1115 (PSB, 5 or 50 μg/site) reversed these beneficial effects. Additionally, BAY application normalized the expression of epidermal barrier proteins, whose integrity is altered in inflammatory skin diseases, while treatment with the antagonist alone worsened it.Our results, besides confirming the anti-inflammatory and antiproliferative effects of the A2BAR agonist, further demonstrate a role of A2BAR activation to preserve the epidermal barrier. Therefore, the activation of A2BAR may constitute a possible new pharmacological target for the treatment of skin inflammatory diseases such as psoriasis.http://www.sciencedirect.com/science/article/pii/S0753332224002853PsoriasisAdenosine A2B receptorEpidermal barrierInvolucrinFilaggrinCaspase-14 |
| spellingShingle | Asunción Marín-Castejón Miguel Marco-Bonilla M. Carmen Terencio Jorge Arasa M. Carmen Carceller M. Luisa Ferrandiz M. Antonia Noguera Rosa Andrés-Ejarque M. Carmen Montesinos Adenosine A2B receptor agonist improves epidermal barrier integrity in a murine model of epidermal hyperplasia Biomedicine & Pharmacotherapy Psoriasis Adenosine A2B receptor Epidermal barrier Involucrin Filaggrin Caspase-14 |
| title | Adenosine A2B receptor agonist improves epidermal barrier integrity in a murine model of epidermal hyperplasia |
| title_full | Adenosine A2B receptor agonist improves epidermal barrier integrity in a murine model of epidermal hyperplasia |
| title_fullStr | Adenosine A2B receptor agonist improves epidermal barrier integrity in a murine model of epidermal hyperplasia |
| title_full_unstemmed | Adenosine A2B receptor agonist improves epidermal barrier integrity in a murine model of epidermal hyperplasia |
| title_short | Adenosine A2B receptor agonist improves epidermal barrier integrity in a murine model of epidermal hyperplasia |
| title_sort | adenosine a2b receptor agonist improves epidermal barrier integrity in a murine model of epidermal hyperplasia |
| topic | Psoriasis Adenosine A2B receptor Epidermal barrier Involucrin Filaggrin Caspase-14 |
| url | http://www.sciencedirect.com/science/article/pii/S0753332224002853 |
| work_keys_str_mv | AT asuncionmarincastejon adenosinea2breceptoragonistimprovesepidermalbarrierintegrityinamurinemodelofepidermalhyperplasia AT miguelmarcobonilla adenosinea2breceptoragonistimprovesepidermalbarrierintegrityinamurinemodelofepidermalhyperplasia AT mcarmenterencio adenosinea2breceptoragonistimprovesepidermalbarrierintegrityinamurinemodelofepidermalhyperplasia AT jorgearasa adenosinea2breceptoragonistimprovesepidermalbarrierintegrityinamurinemodelofepidermalhyperplasia AT mcarmencarceller adenosinea2breceptoragonistimprovesepidermalbarrierintegrityinamurinemodelofepidermalhyperplasia AT mluisaferrandiz adenosinea2breceptoragonistimprovesepidermalbarrierintegrityinamurinemodelofepidermalhyperplasia AT mantonianoguera adenosinea2breceptoragonistimprovesepidermalbarrierintegrityinamurinemodelofepidermalhyperplasia AT rosaandresejarque adenosinea2breceptoragonistimprovesepidermalbarrierintegrityinamurinemodelofepidermalhyperplasia AT mcarmenmontesinos adenosinea2breceptoragonistimprovesepidermalbarrierintegrityinamurinemodelofepidermalhyperplasia |