Purinergic Signalling

, Volume 13, Issue 4, pp 405–415 | Cite as

The P2X7 receptor is not essential for development of imiquimod-induced psoriasis-like inflammation in mice

  • Nicholas J. Geraghty
  • Kylie J. Mansfield
  • Stephen J. Fuller
  • Debbie Watson
  • Ronald Sluyter
Original Article
First Online:
Received:
Accepted:

Abstract

Psoriasis is a chronic inflammatory skin disorder, characterised by epidermal hyperplasia (acanthosis) and leukocyte infiltration of the skin. Current therapies are inadequate, highlighting the need for new therapeutic targets. The P2X7 receptor is implicated in the pathogenesis of psoriasis. This study investigated the role of P2X7 in imiquimod (IMQ)-induced psoriasis-like inflammation. Topically applied IMQ caused twofold greater ear swelling in BALB/c mice compared to C57BL/6 mice, which encode a partial loss-of-function missense mutation in the P2RX7 gene. However, there was no difference in histological skin pathology (acanthosis and leukocyte infiltration) between the two strains. IMQ treatment up-regulated P2X7 expression in skin from both mouse strains. Additionally, IMQ induced ATP release from cultured human keratinocytes, a process independent of cell death. Injection of the P2X7 antagonist Brilliant Blue G (BBG) but not A-804598 partly reduced ear swelling compared to vehicle-injected control mice. Neither antagonist altered skin pathology. Moreover, no difference in ear swelling or skin pathology was observed between C57BL/6 and P2X7 knock-out (KO) mice. Flow cytometric analysis of IMQ-treated skin from C57BL/6 and P2X7 KO mice demonstrated similar leukocyte infiltration, including neutrophils, macrophages and T cells. In conclusion, this study demonstrates that P2X7 is not essential for development of IMQ-induced psoriasis-like inflammation but does not exclude a role for this receptor in psoriasis development in humans or other mouse models of this disease.

Keywords

P2X7 receptor Extracellular ATP Imiquimod Psoriasis Skin immune system 
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Notes

Acknowledgements

The authors thank Vanessa Sluyter (University of Wollongong, Wollongong, Australia) and Illawarra Health and Medical Research Institute (Wollongong, Australia) technical and animal staff for technical support. The authors also thank Chao Deng, Blagojce Jovcevski (both University of Wollongong) and Scott Byrne (University of Sydney, Sydney, Australia) for their helpful advice and iNova Pharmaceuticals for kindly donating some Aldara™ cream samples.

This project was funded by the Faculty of Science, Medicine and Health, University of Wollongong. NJ Geraghty is supported through an Australian Government Research Training Program Scholarship. D Watson is supported by AMP’s Tomorrow Fund. D Watson and R Sluyter receive additional support from the Centre for Medical and Molecular Bioscience, University of Wollongong.

Compliance with ethical standards

Conflict of interest

Nicholas J Geraghty declares that he has no conflict of interest.

Kylie J Mansfield declares that she has no conflict of interest.

Stephen J Fuller declares that he has no conflict of interest.

Debbie Watson declares that she has no conflict of interest.

Ronald Sluyter declares that he has no conflict of interest.

Ethical approval

All animal experiments were conducted under protocol AE14/10, which was approved by the University of Wollongong Animal Ethics Committee (Wollongong, Australia).

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Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  1. 1.School of Biological SciencesUniversity of WollongongWollongongAustralia
  2. 2.Centre for Medical and Molecular BioscienceUniversity of WollongongWollongongAustralia
  3. 3.Illawarra Health and Medical Research InstituteWollongongAustralia
  4. 4.School of MedicineUniversity of WollongongWollongongAustralia
  5. 5.Sydney Medical SchoolUniversity of SydneySydneyAustralia

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