Adenosine A_2A and A_2B Receptors Differentially Modulate Keratinocyte Proliferation: Possible Deregulation in Psoriatic Epidermis

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• 作者：Rosa M. André ; s¹ ; ² ; Marí ; a Carmen Terencio¹ ; ² ; Jorge Arasa¹ ; ² ; Miguel Payá ; ¹ ; ² ; Francisca Valcuende-Cavero³ ; ⁴ ; Pedro Navaló ; n⁵ ; Marí ; a Carmen Montesinos¹ ; ² ; ^{m.carmen.montesinos@uv.es}
• 关键词：AR ; adenosine receptors ; BAY ; BAY60&ndash ; 6583 ; CGS ; CGS-21680 ; iCa2+ ; intracellular calcium ; MRS ; MRS-1706 ; MTT ; 3-(4 ; 5-dimethylthiazol-2-yl)-2 ; 5-diphenyltetrazolium bromide ; NECA ; 5'-N-ethylcarboxamidoadenosine ; NHEK ; normal human epidermal keratinocyte ; SCH ; SCH-442416 ; TNF ; tumor necrosis factor ; TPA ; 12-O-tetradecanoylphorbol-13-acetate
• 刊名：Journal of Investigative Dermatology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：137
• 期：1
• 页码：123-131
• 全文大小：650 K
• 卷排序：137

文摘

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.