Anales RANF

P.78 ADENOSINE A 2B RECEPTOR ACTIVATION IMPROVES EPIDERMAL BARRIER INTEGRITY DAMPENED BY INFLAMMATION M. Marco 1 , A. Marín-Castejón 1 , R.M. Andrés, J. Arasa, M.C. Terencio 1 , M.C. Montesinos 1 1 . University of Valencia, Valencia, Spain. The integrity of the skin barrier is compromised in psoriasis due to the increased proliferation and aberrant differentation of keratinocytes, the main cellular type in epidermis. Recent studies have shown that A 2B is the most expressed adenosine receptor in human keratinocytes, being able to regulate epidermal proliferation and inflammatory response. Proteins like filaggrin, loricrin and involucrin play and important role in the maintenance of barrier function. In the present study we determine the involvement of A 2B receptors regarding epidermis integrity in the mouse skin hyperplasia induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). The A 2B R agonist BAY60-6583 (BAY) (1 µg/site), the A 2B R antagonist PSB-1115 (5µg/site), and both together were applied on the shaved backs of female Swiss mice 30 minutes before TPA (2nmol/site) for three consecutive days. On day four, animals were sacrificed and 1 cm 2 punch biopsies were collected and processed for immunochemistry assays. Treatment with the A 2B antagonist PSB worsened the severity of TPA-induced skin lesions whereas BAY markedly ameliorated them. The immunohistochemical analysis showed that the expression of both, filaggrin and loricrin, was decreased after treatment with either PSB, the stimulus TPA, or their combination, compared to naïve mice. In contrast, application of BAY enhanced the expression of these proteins within the epidermis. Besides, BAY improved the TPA-induced aberrant expression of involucrin in stratum corneum, effect that was abrogated by the antagonist PSB. These results demonstrate the beneficial role of A 2B receptor in regulating epidermal integrity and show the interest of this receptor as a potential pharmacological target in the treatment of pathologies where excessive inflammatory response may affect to the skin’s architecture such as psoriasis.