Publication
Title
B₁ and B₂ kinin receptor blockade improves psoriasis-like disease
Author
Abstract
Background and Purpose The entire kallikrein-kinin system is present in the skin, and it is thought to exert a relevant role in cutaneous diseases, including psoriasis. The present study was designed to evaluate the relevance of kinin receptors in the development and progression of a model of psoriasis in mice. Experimental Approach The effects of kinin B-1 and B-2 receptor knockout and of kinin receptor antagonists (SSR240612C or FR173657) were assessed in a model of psoriasis induced by imiquimod in C57BL/6 mice. Severity of psoriasis was assessed by histological and immunohistochemical assays of skin, along with objective scores based on the clinical psoriasis area and severity index. Key Results Both kinin receptors were up-regulated following 6 days of imiquimod treatment. Kinin B-1 and B-2 receptor deficiency and the use of selective antagonists show morphological and histological improvement of the psoriasis hallmarks. This protective effect was associated with a decrease in undifferentiated and proliferating keratinocytes, decreased cellularity (neutrophils, macrophages, and CD4(+) T lymphocytes), reduced gamma delta T cells, and lower accumulation of IL-17. The lack of B-2 receptors resulted in reduced CD8(+) T cells in the psoriatic skin. Relevantly, blocking kinin receptors reflected the improvement of psoriasis disease in the well-being behaviour of the mice. Conclusions and Implications Kinins exerted critical roles in imiquimod-induced psoriasis. Both B-1 and B-2 kinin receptors exacerbated the disease, influencing keratinocyte proliferation and immunopathology. Antagonists of one or even both kinin receptors might constitute a new strategy for the clinical treatment of psoriasis.
Language
English
Source (journal)
British journal of pharmacology. - London
Publication
London : 2020
ISSN
0007-1188
DOI
10.1111/BPH.15077
Volume/pages
177 :15 (2020) , p. 3535-3551
ISI
000536161300001
Pubmed ID
32335893
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Publication type
Subject
External links
Web of Science
Record
Identifier
Creation 09.04.2024
Last edited 10.04.2024
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