ACTION SPECTRA FOR THE trans TO cis PHOTOISOMERISATION OF UROCANIC ACID in vitro and IN MOUSE SKIN

Abstract

Urocanic acid (UCA) is a major UV chromophore in the upper layers of the skin where it is found predominantly as the trans isomer. UV irradiation induces photoisomerisation of trans-UCA to cis-UCA which has been shown to mimic some of the immunosuppressive properties of UV exposure. We examined the wavelength dependence for trans-UCA to cis-UCA photoisomerisation in vitro and in mouse skin in vivo over the spectral range 270-340 nm. The resulting action spectra were very similar with maximal effectiveness at 300-315 nm and equal activity at 270 nm and 325-330 nm, demonstrating that UVA-II radiation (320-340 nm) is efficient at UCA photoisomerisation. These action spectra differed markedly from the trans-UCA absorption spectrum in vitro and also the reported action spectrum for UV suppression of contact hypersensitivity in mice. These findings suggest that the relationship between cis-UCA formation in skin and UV-induced immunosuppression may be complex.

Chromophore for UV‐lnduced Immunosuppression: Urocanic Acid

“…Indeed, when weighted for the solar spectral output, the most effective photoisomerization wavelength in human skin is 326 nm (3). In addition the action spectrum for the isomerization of UCA in mouse skin in vivo has been constructed and has a peak of 300-310 nm (4). Therefore the relationship between the formation of cis-UCA and effects on the immune system is likely to be complex and may involve, for example, a cascade of responses initiated by the isomerization or cis-UCA acting at a site other than the site of isomerization.…”

“…The development of these tumors presumably results from transforming events induced in keratinocyte targets as a consequence of exposure to UVR. However, work over the past two decades has demonstrated that, at least in mice, most UVR-induced skin tumors are highly immunogenic and regress upon transfer to syngeneic recipients (3,4). This, of course, raises the question as to why these tumors develop and grow in the primary host.…”

“…In mice exposed to doses of UVR sufficient to induce skin tumors, if the tumor is surgically removed, the primary host is susceptible to retransplantation of its own tumor although normal syngeneic mice will reject the majority of these tumors (3,4). Interestingly, the exposure of mice to UVR, even subcarcinogenic, although substantial doses, leads to a state of susceptibility to transplanted tumors.…”

“…Interestingly, the exposure of mice to UVR, even subcarcinogenic, although substantial doses, leads to a state of susceptibility to transplanted tumors. Upon transfer of lymphoid cells from tumor-bearing or nontumor-bearing UVR-exposed donors, naive mice become susceptible to the growth of transplanted UVR-induced skin tumors (3,4). The cells responsible for this susceptibility have been shown to be T cells and have been termed T suppresser cells because they appear to suppress the immune-mediated rejection of the transplanted tumor.…”

UVB-Shielding Effects of para-Coumaric Acid

“…Of these compounds, UCA has attracted an attention in dermatology and cosmetics fields as a natural sunscreen since it was identified as the major acid-soluble, UVabsorbing compound in the stratum corneum [19,20]. 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].…”