| Autor: |
Arasa, Jorge, Martos, Patricio, Terencio, María Carmen, Valcuende‐Cavero, Francisca, Montesinos, María Carmen |
| Předmět: |
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| Zdroj: |
Experimental Dermatology; Aug2014, Vol. 23 Issue 8, p555-560, 6p |
| Abstrakt: |
The nucleoside adenosine is a known regulator of immunity and inflammation that mediates, at least in part, the anti-inflammatory effect of methotrexate, an immunosuppressive agent widely used to treat autoimmune inflammatory diseases. Adenosine A2A receptors play a key role in the inhibition of the inflammatory process besides promoting wound healing. Therefore, we aimed to determine the topical effect of a selective agonist, CGS-21680, on a murine model of skin hyperplasia with a marked inflammatory component. Pretreatment with either CGS-21680 (5 μg per site) or the reference agent dexamethasone (200 μg/site) prevented the epidermal hyperplasia and inflammatory response induced by topical application of 12-O-tetradecanoylphorbol-13-acetate ( TPA, 2 nmol/site) for three consecutive days. The histological analysis showed that both CGS-21680 and dexamethasone produced a marked reduction of inflammatory cell infiltrate, which correlated with diminished myeloperoxidase ( MPO) activity in skin homogenates. Both treatments reduced the levels of the chemotactic mediators LTB4 and CXCL-1, and the inflammatory cytokine TNF- α, through the suppression of NF κB phosphorylation. The immunohistochemical analysis of the hyperproliferative markers cytokeratin 6 ( CK6) and Ki67 revealed that while both agents inhibit the number of proliferating cells in the epidermis, CGS-21680 treatment promoted dermal fibroblasts proliferation. Consistently, increased collagen deposition in dermis was observed in tissue sections from agonist-treated mice. Our results showed that CGS 21680 efficiently prevents phorbol-induced epidermal hyperplasia and inflammation in mice without the deleterious atrophic effect of topical corticosteroids. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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