Topical Urocanic Acid Enhances Uv‐induced Tumour Yield and Malignancy in the Hairless Mouse

Reeve, Vivienne E.; Greenoak, Gavin E.; Canfield, P. J.; Boehm‐Wilcox, Christa; Gallagher, C. H.

doi:10.1111/j.1751-1097.1989.tb09195.x

Cited by 83 publications

(43 citation statements)

References 22 publications

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“…The inhibitory effect of cis-UCA on tumor Ag presentation by LC as well as the elevated concentrations of cis-UCA within the skin after UV treatment (13,34) suggest that cis-UCA may play a role in the development of UV-induced skin cancer. Accordingly, topical application of UCA, followed by chronic UVB exposure resulted in augmented skin tumor development (12). These data clearly indicated that cis-UCA can promote photocarcinogenesis.…”

Section: Neutralization Of Endogenous Cis-uca By Anti-cis-uca Ab Treamentioning

confidence: 71%

“…In addition, systemic application of cis-UCA prolonged allograft survival in mice (11). Topically applied trans-UCA in combination with chronic UVR treatment resulted in enhanced photocarcinogenesis in mice, indicating that cis-UCA may be involved in the generation of UV-induced skin cancer probably by causing immunosuppression (12). To this end, previous investigations by our group have shown that cis-but not trans-UCA inhibits the ability of Langerhans cells (LC), the primary APC in the skin, to present tumor Ag (TA), both for the induction and elicitation of antitumoral immune responses in mice (13).…”

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confidence: 99%

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IL-12 Prevents the Inhibitory Effects of cis-Urocanic Acid on Tumor Antigen Presentation by Langerhans Cells: Implications for Photocarcinogenesis

Beissert

Rühlemann

Mohammad

et al. 2001

The Journal of Immunology

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UV radiation induces skin cancer primarily by its DNA-damaging properties, but also by its capacity to suppress the immune system. The photoisomer of urocanic acid (UCA), cis-UCA, is an important mediator of UV-induced immunosuppression and is involved in the inhibition of tumor immunity. The immunomodulatory cytokine IL-12 is known to counteract many of the immunosuppressive effects of UV radiation, including UV-induced immune tolerance. In this study, we addressed whether IL-12 also reverts the immunosuppressive activities of cis-UCA. Cis-UCA inhibits the ability of Langerhans cells to present tumor Ags for primary and secondary tumor immune responses. IL-12 treatment completely prevented the suppression by cis-UCA. IL-12 also protected mice from cis-UCA-induced suppression of contact hypersensitivity responses. To study the effects of cis-UCA on Ag-processing and Ag-presenting function in vitro, Langerhans cells were treated with UCA isomers and incubated with OVA or OVA peptide323–339 before exposure to OVA-specific transgenic T cells. Cis-, but not trans-UCA suppressed Ag presentation, which was completely reversed upon addition of IL-12. Since these findings suggest that cis-UCA may play an important role in photocarcinogenesis by inhibiting a tumor immune response, mice were chronically UVB irradiated to induce skin cancer. Whereas all mice in the control groups developed tumors, mice treated with a mAb with specificity for cis-UCA showed a significantly reduced tumor incidence. These data strongly indicate the importance of cis-UCA during photocarcinogenesis and support the concept of counteracting cis-UCA as an alternative strategy to prevent UV-induced skin cancer, possibly via the application of IL-12.

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Section: Neutralization Of Endogenous Cis-uca By Anti-cis-uca Ab Treamentioning

confidence: 71%

mentioning

confidence: 99%

IL-12 Prevents the Inhibitory Effects of cis-Urocanic Acid on Tumor Antigen Presentation by Langerhans Cells: Implications for Photocarcinogenesis

Beissert

Rühlemann

Mohammad

et al. 2001

The Journal of Immunology

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“…In previous studies, mice were unrestrained as they underwent whole-body irradiation with UVB [24,33]. In those types of experimental conditions, each animal could be irradiated with different doses of UVB, which might contribute to the large experimental errors.…”

Section: Discussionmentioning

confidence: 99%

“…The photon energy absorbed by UCA is effectively dissipated through the reversible isomerization to cis-urocanic acid [21,22]. However, UCA's reputation as an ideal natural sunscreen was shattered by the observations that cis-urocanic acid mediated the immunosuppressive effect of UV [23], and UCA increased the photocarcinogenic risk in hairless mice [24]. In contrast, Barresi and colleagues observed that histidase-deficient mice were more susceptible to UV-induced DNA damage and apoptosis than wild type mice [25].…”

Section: Introductionmentioning

confidence: 99%

UVB-Shielding Effects of para-Coumaric Acid

Song¹,

Boo²

2012

Journal of the Society of Cosmetic Scientists of Korea

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Recent studies have uncovered attractive properties of para-coumaric acid (PCA) as a potential skin hywhitening agent. The purpose of the current study was to examine its UVB-shielding effects. Effects of PCA on the viability of HaCaT cells exposed to UVB were assessed in vitro in comparison with other aromatic amino acid metabolites that have similar UV absorption spectra. For in vivo test, PCA cream (1.5 %) and cream base were topically applied to the dorsal skin of SKH-1 hairless mice and the inflammatory responses due to UVB exposure were monitored by changes in skin color (erythema) and thickness (edema). The cream application-UVB exposure regimen was repeated every other day for a total of 12 sessions. When HaCaT cells were irradiated with UVB, there was a dose-dependent decline in cell viability. The cell viability decline due to UVB exposure (10 mJ cm -2 ) was significantly prevented by 100 µM PCA, cinnamic acid, urocanic acid, or indole acrylic acid by 39, 27, 39, or 31 %, respectively. Topical application of PCA cream onto the dorsal skin of hairless mice (10 µg cm -2 ) attenuated the changes of color parameters, L*, a*, b* values, and thickness of the UVB (150 mJ cm -2 )-exposed skin by 59, 50, 58, and 53 %, respectively. The current study, together with the previous studies that demonstrated the antimelanogenic effects of PCA, suggested that PCA may prevent not only dyspigmentation but also inflammatory reactions in the UVB-exposed skin.

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“…It does not, however, inhibit mitogen-induced lymphocyte transformation (47). Additionally, topical cis-UCA treatment enhances UVR-induced tumor yield in hairless mice (48). This area is complicated, however, by the recent report that exposure of mice to UVA I1 ( 3 6 0 4 0 0 nm) radiation produces as much cis-UCA in the epidermis as UVB radiation but does not lead to suppression of DTH (49).…”

Section: Photoreceptors For Uvr-induced Immunsuppressionmentioning

confidence: 77%