cis-Urocanic acid attenuates acute dextran sodium sulphate-induced intestinal inflammation.
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.
Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Eric
E
Albert
John
J
Walker
Aducio
A
Thiesen
Thomas
T
Churchill
Karen
K
Madsen
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000517:prevention & control*; D016264:Dextran Sulfate / Q000009:adverse effects*; D005434:Flow Cytometry; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D014560:Urocanic Acid / Q000494:pharmacology*
D016753:Interleukin-10; D016264:Dextran Sulfate; D014560:Urocanic Acid