Adenosine A2A and A2B Receptors Differentially Modulate Keratinocyte Proliferation: Possible Deregulation in Psoriatic Epidermis
| Autor: | Pedro Navalón, María Carmen Terencio, María Carmen Montesinos, Jorge Arasa, Rosa María Hernández Andrés, Francisca Valcuende-Cavero, Miguel Payá |
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| Rok vydání: | 2017 |
| Předmět: |
keratinocytes
0301 basic medicine medicine.medical_specialty Adenosine psoriatic epidermis Dermatology Biology Biochemistry 03 medical and health sciences chemistry.chemical_compound Internal medicine medicine Receptor Molecular Biology CGS-21680 human epidermal keratinocytes MRS-1706 Cell Biology Purinergic signalling Adenosine A3 receptor Adenosine receptor Cell biology 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry Keratinocyte medicine.drug |
| Zdroj: | Repositori Universitat Jaume I Universitat Jaume I |
| ISSN: | 0022-202X |
| Popis: | Adenosine is a potent regulator of inflammation and immunity, but the role of adenosine receptors in keratinocytes remains controversial. We determined that in addition to A2B receptors, human epidermal keratinocytes also express A2A receptors, although to a lower extent. Through the use of selective adenosine receptor agonists and antagonists, we showed that physiological concentrations of adenosine activate A2B receptors in normal human keratinocytes, inducing cell cycle arrest through the increase of intracellular calcium but not through cAMP signaling. In contrast, the selective activation of A2A receptors by CGS-21680 induces keratinocyte proliferation via p38–mitogen-activated protein kinase activation. Adenosine and selective A2A and A2B agonists presented anti-inflammatory profiles independent of adenosine receptors but mediated by membrane phosphatase activation. Finally, keratinocyte exposure to diverse inflammatory cytokines altered adenosine receptor expression by reducing A2B and increasing A2A, a pattern also observed in psoriatic epidermis. Because increased epidermal turnover and inflammatory response are characteristics of psoriatic disease, further studies are needed to assess the role and consequences of the altered adenosine receptor expression in lesional and nonlesional psoriatic keratinocytes. We thank Laura Catalán for her technical assistance in the immunoblotting analysis. This work was supported by the Spanish Ministry of Economy and Competitiveness, ISCIII, FEDER (SAF2009-10347 and RETICEF RD07/0013/ 2011), the University of Valencia (AEVI 2015-16) and the Spanish Conselleria Valenciana d’Educació (Prometeo 2010-047). Rosa M. Andrés was the recipient of a research fellowship from the Spanish Conselleria Valenciana d’Educació. |
| Databáze: | OpenAIRE |
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