Document Detail

Inhibition of UV-induced uric acid production using Allopurinol prevents suppression of the contact hypersensitivity response.
MedLine Citation:
PMID:  23387472     Owner:  NLM     Status:  Publisher    
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 NLRP3 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 NLRP3-inflammasome. However, in contrast to NLRP3, the adaptor protein ASC, which is required for formation of the NLRP3-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.
Sarah Leighton; Lai-Fong Kok; Gary M Halliday; Scott N Byrne
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-20
Journal Detail:
Title:  Experimental dermatology     Volume:  -     ISSN:  1600-0625     ISO Abbreviation:  Exp. Dermatol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-2-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9301549     Medline TA:  Exp Dermatol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 John Wiley & Sons A/S.
Discipline of Infectious Diseases and Immunology, Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Discipline of Dermatology, Bosch Institute, Faculty of Medicine, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
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