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Inhibition of UV ‐induced uric acid production using A llopurinol prevents suppression of the contact hypersensitivity response
Author(s) -
Leighton Sarah,
Kok LaiFong,
Halliday Gary M.,
Byrne Scott N.
Publication year - 2013
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12096
Subject(s) - uric acid , inflammasome , allopurinol , immune system , chemistry , in vivo , biochemistry , immunology , receptor , medicine , biology , microbiology and biotechnology
Exposure to solar ultraviolet ( UV ) radiation suppresses adaptive immune responses. This contributes to skin carcinogenesis but may protect from some autoimmune diseases. However, the molecular changes occurring within UV ‐exposed skin that precipitate the downstream events leading to immune suppression are not fully understood. Using a combination of in vitro and in vivo mouse models, we have discovered that UV induces significant cutaneous production of immune suppressive uric acid. The ability of UV ‐induced uric acid to inhibit a contact hypersensitivity response was successfully blocked by the gout‐treating drug Allopurinol. Up‐regulation of NLRP 3 mRNA by UV was also found to be dependent on UV ‐induced uric acid. This suggested that the target of UV ‐induced uric acid included proteins involved in the formation and activation of the NLRP 3‐inflammasome. However, in contrast to NLRP 3, the adaptor protein ASC , which is required for formation of the NLRP 3‐inflammasome, was significantly down‐regulated. Furthermore, this down‐regulation was not dependent on UV ‐induced uric acid production because Allopurinol treatment failed to prevent the reduction in ASC . Hence, our results identify uric acid as an important molecule involved in sterile UV ‐induced inflammation and immune suppression. UV‐induced uric acid may therefore offer a unique therapeutic target for preventing and treating skin cancer.