Article

cis-Urocanic Acid Attenuates Acute Dextran Sodium Sulphate-Induced Intestinal Inflammation

Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
PLoS ONE (Impact Factor: 3.53). 10/2010; 5(10):e13676. DOI: 10.1371/journal.pone.0013676
Source: PubMed

ABSTRACT 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.

Download full-text

Full-text

Available from: Karen Madsen, Aug 12, 2015
0 Followers
 · 
97 Views
  • Source
    • "Both have shown to have anti-inflammatory effects both in vivo and in vitro [14] [15] [16]. In the case of cis-UCA, attenuation of experimental colonic epithelial damage, induced by dextran sodium sulfate (DSS), has recently been obtained in vivo [17]. Urocanic acid (UCA) derivatives, studied here, are natural and synthetic derivatives of UCA. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Urocanic acid (UCA) derivatives were tested for their anti-inflammatory activity in inflammatory bowel disease (IBD) in two models: ex vivo and an experimental mouse model. Ex vivo: inflamed colonic tissue was incubated in culture medium with or without the UCA derivatives. Biopsies, incubated with UCA derivatives, produced lower levels of proinflammatory cytokines IL-6 and IL-8 as compared to control biopsies. The same compounds also showed increased levels of IL-10, providing an additional indication for anti-inflammatory properties. In vivo: a combination of two imidazoles and a combination of two of their ethyl esters were administered to mice while colitis was induced by oral administration of dextran sodium sulfate (DSS). Some parameters did not show conclusive effects, but the imidazoles and their ethyl esters reduced the area of inflammation and the number of infiltrating neutrophils. Fibrosis and the sum of all histological aspects were reduced by the imidazoles, whereas the ethyl esters reduced the colon weight to length ratio. These results suggest that the UCA derivatives have anti-inflammatory effect on IBD. In addition, fine tuning of the ex vivo model may provide an elegant way to predict anti-inflammatory effects of potential drugs in humans, which may decrease the need for animal experiments.
    09/2012; 2012:898153. DOI:10.5402/2012/898153
  • Source
    • "Interestingly, cis‐urocanic acid (produced after UV radiation) is well known to be an immune‐ suppressor (Gibbs et al., 2008) and it has been considered for the topical treatment of inflammatory and autoimmune diseases of skin (Ong, 2009). A recent publication showed how cis‐urocanic acid can also influence distal sites of inflammation, reducing the severity of colitis in a mouse model (Albert et al., 2010). These considerations can provide a scientific explanation to many old anecdotes on the benefits of sun exposure in asthma treatment (Gorman et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Asthma is a heterogeneous disorder and one of the most common chronic childhood diseases. An improved characterization of asthma phenotypes would be invaluable for the understanding of the pathogenic mechanisms and the correct treatment of this disease. The aim of this pilot study was to explore the potential of metabolomics applied to urine samples in characterizing asthma, and to identify the most representative metabolites. Urine samples of 41 atopic asthmatic children (further subdivided in sub-groups according to the symptoms) and 12 age-matched controls were analyzed. Untargeted metabolic profiles were collected by LC-MS, and studied by multivariate analysis. The group of the asthmatics was differentiated by a model that proved to be uncorrelated with the chronic assumption of controller drugs on the part of the patients. The distinct sub-groups were also appropriately modeled. Further investigations revealed a reduced excretion of urocanic acid, methyl-imidazoleacetic acid and a metabolite resembling the structure of an Ile-Pro fragment in the asthmatics. The meaning of these findings was discussed and mainly correlated with the modulation of immunity in asthma. Metabolic profiles from urines have revealed the potential to characterize asthma and enabled the identification of metabolites that may have a role in the underlying inflammation.
    Biomedical Chromatography 01/2012; 26(1):89-94. DOI:10.1002/bmc.1631 · 1.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Humans obtain most of their vitamin D through the exposure of skin to sunlight. The immunoregulatory properties of vitamin D have been demonstrated in studies showing that vitamin D deficiency is associated with poor immune function and increased disease susceptibility. The benefits of moderate ultraviolet (UV) radiation exposure and the positive latitude gradients observed for some immune-mediated diseases may therefore reflect the activities of UV-induced vitamin D. Alternatively, other mediators that are induced by UV radiation may be more important for UV-mediated immunomodulation. Here, we compare and contrast the effects of UV radiation and vitamin D on immune function in immunopathological diseases, such as psoriasis, multiple sclerosis and asthma, and during infection.
    Nature Reviews Immunology 08/2011; 11(9):584-96. DOI:10.1038/nri3045 · 33.84 Impact Factor
Show more