title: Adenosine A2Aand A2BReceptors Differentially Modulate Keratinocyte Proliferation: Possible Deregulation in Psoriatic Epidermis.
abstract: 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 A2Breceptors, human epidermal keratinocytes also express A2Areceptors, although to a lower extent. Through the use of selective adenosine receptor agonists and antagonists, we showed that physiological concentrations of adenosine activate A2Breceptors 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 A2Areceptors by CGS-21680 induces keratinocyte proliferation via p38-mitogen-activated protein kinase activation. Adenosine and selective A2Aand A2Bagonists 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 A2Band 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.
authors: Departament of Pharmacology, Faculty of Pharmacy, University of Valencia, Valencia, Spain; Institute of Molecular Recognition and Technological Development (IDM), Valencia, Spain.
authors: Rosa M
authors: RM
authors: Andrés
authors: Departament of Pharmacology, Faculty of Pharmacy, University of Valencia, Valencia, Spain; Institute of Molecular Recognition and Technological Development (IDM), Valencia, Spain.
authors: María Carmen
authors: MC
authors: Terencio
authors: Departament of Pharmacology, Faculty of Pharmacy, University of Valencia, Valencia, Spain; Institute of Molecular Recognition and Technological Development (IDM), Valencia, Spain.
authors: Jorge
authors: J
authors: Arasa
authors: Departament of Pharmacology, Faculty of Pharmacy, University of Valencia, Valencia, Spain; Institute of Molecular Recognition and Technological Development (IDM), Valencia, Spain.
authors: Miguel
authors: M
authors: Payá
authors: Department of Dermatology, University Hospital La Plana, Vila-real, Spain; Predepartamental Unit of Medicine, Universitat Jaume I, Castellón, Spain.
authors: Francisca
authors: F
authors: Valcuende-Cavero
authors: Department of Urology, General University Hospital of Valencia, Valencia, Spain.
authors: Pedro
authors: P
authors: Navalón
authors: Departament of Pharmacology, Faculty of Pharmacy, University of Valencia, Valencia, Spain; Institute of Molecular Recognition and Technological Development (IDM), Valencia, Spain. Electronic address: m.carmen.montesinos@uv.es.
authors: María Carmen
authors: MC
authors: Montesinos
mesh_terms: D000704:Analysis of Variance; D001707:Biopsy, Needle; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011565:Psoriasis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology*; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology*; D043682:Receptor, Adenosine A1 / Q000187:drug effects / Q000378:metabolism; D043683:Receptors, Adenosine A2 / Q000187:drug effects / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: D016207:Cytokines; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D043683:Receptors, Adenosine A2