B1 and B2 kinin receptor participation in hyperproliferative and inflammatory skin processes in mice
Abstract Background Kinins are released during dermal injury and inflammation and seem to contribute to the pathogenesis of cutaneous diseases. Objective Participation of kinins in skin inflammatory process was evaluated using knockout mice and non-peptide kinin receptor antagonists. Methods Chronic...
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Published in | Journal of dermatological science Vol. 64; no. 1; pp. 23 - 30 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
01.10.2011
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Subjects | |
Online Access | Get full text |
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Summary: | Abstract Background Kinins are released during dermal injury and inflammation and seem to contribute to the pathogenesis of cutaneous diseases. Objective Participation of kinins in skin inflammatory process was evaluated using knockout mice and non-peptide kinin receptor antagonists. Methods Chronic skin inflammation was induced by multiple applications of TPA in mice ear. Results The B2 knockout mice (B2−/− ) showed a significant increase of ear weight (23 ± 10%) and epidermal cellular hyperproliferation and acanthosis formation upon histological analysis when compared with wildtype mice. Also, evaluation of PCNA levels by Western blot and immunohistochemistry confirmed the increase in the epidermis hyperproliferation in the ear skin of B2−/− mice. In contrast, no modification in these parameters was detected in B1 knockout mice (B1−/− ). However, mice lacking both kinin receptors (B1 B2−/− ) presented a considerable reduction of epidermis thickness and in PCNA levels. Following the establishment of skin inflammation (5th day of TPA application) treatment with the non-peptide antagonists SSR 240612 (B1 receptor antagonist), FR 173657 (B2 receptor antagonist), or SSR 240612 plus FR 173657 topically applied, caused a significant inhibition of ear weight (20 ± 5%, 34 ± 4% and 32 ± 6%, respectively). In the histological analysis, the antagonists produced a reduction in epidermal hyperplasia and acanthosis formation; but the treatment with a combination of the two antagonists did not increase efficacy. Conclusion Kinin receptors seem to be involved in the control of the keratinocyte hyperproliferative process, and non-peptide kinin receptor antagonists may be useful tools in the treatment of hyperproliferative skin disorders. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0923-1811 1873-569X |
DOI: | 10.1016/j.jdermsci.2011.06.016 |