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B(1) and B(2) kinin receptor blockade improves psoriasis-like disease

Authors

  • B. da Silva Soley
  • L.M. Silva
  • D.A.G.B. Mendes
  • A. Báfica
  • J.B. Pesquero
  • M. Bader
  • D.A. Witherden
  • W.L. Havran
  • J.B. Calixto
  • M.F. Otuki
  • D.A. Cabrini

Journal

  • British Journal of Pharmacology

Citation

  • Br J Pharmacol 177 (15): 3535-3551

Abstract

  • BACKGROUND AND PURPOSE: Evidence indicates that the entire kallikrein‐kinin system is present in the skin, and it is thought to exert a relevant role in cutaneous diseases, including psoriasis. Thus, the present study was designed to evaluate the relevance of kinin receptors in the development and progression of a psoriasis mice model. EXPERIMENTAL APPROACH: Kinin B(1) and B(2) receptor knockout mice as well as C57BL/6 wild type (WT) mice treated with kinin receptor antagonists (SSR240612C or FR173657) were submitted to the Imiquimod (IMQ)‐induced psoriasis model. KEY RESULTS: Both kinin receptors were upregulated following 6 days of IMQ treatment. Kinin B(1) and B(2) receptor deficiency as well as 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, CD4(+) T lymphocytes), reduced γδ T cells as well as 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: The present results have provided clear experimental evidence that kinins exert a critical role in IMQ‐induced psoriasis. Both B(1) and B(2) kinin receptors exacerbate the disease development, influencing keratinocyte proliferation and immunopathology. Therefore, the use of antagonists for one or even both kinin receptors might constitute a new strategy for psoriasis clinical treatment.


DOI

doi:10.1111/bph.15077