On exposure to sunlight,
urocanic acid (UCA) in the skin is converted from trans to the cis form and distributed systemically where it confers systemic immunosuppression. The aim of this study was to determine if administration of cis-UCA would be effective in attenuating
colitis and the possible role of
IL-10.
Colitis was induced in 129/SvEv mice by administering 5%
dextran sodium sulfate (DSS) for 7 days in
drinking water. During this period mice received daily subcutaneously
injections of cis-UCA or vehicle. To examine a role for
IL-10, 129/SvEv IL-10(-/-) mice were injected for 24 days with cis-UCA or vehicle. Clinical disease was assessed by measurement of
body weight, stool consistency, and presence of blood. At sacrifice, colonic tissue was collected for histology and measurement of
myeloperoxidase and
cytokines. Splenocytes were analyzed for CD4+CD25+FoxP3+ T-regulatory cells via flow cytometry. Murine bone-marrow derived antigen-presenting cells were treated with
lipopolysaccharide (LPS) ± UCA and
cytokine secretion measured. Our results demonstrated that cis-UCA at a dose of 50 µg was effective in ameliorating DSS-induced
colitis as evidenced by reduced
weight loss and attenuated changes in colon weight/length. This protection was associated with reduced colonic expression of CXCL1, an increased expression of
IL-17A and a significant preservation of splenic CD4+CD25+FoxP3+ T-regulatory cells. cis-UCA decreased LPS induced CXCL1, but not TNFα secretion, from antigen-presenting cells in vitro. UCA reduced colonic levels of IFNγ in IL-10(-/-) mice but did not attenuate
colitis. In conclusion, this study demonstrates that cis-
urocanic acid is effective in reducing the severity of
colitis in a chemically-induced mouse model, indicating that pathways induced by ultraviolet radiation to the skin can influence distal sites of
inflammation. This provides further evidence for a possible role for sunlight exposure in modulating inflammatory disorders.