An Action Spectrum for the Production of cis-Urocanic Acid in Human Skin In Vivo

Abstract

Urocanic acid (UCA) is present at millimolar concentrations in mammalian epidermis and undergoes photoisomerization from the naturally occurring trans-isomer to the cis-isomer on exposure to ultraviolet radiation (UVR). Cis-UCA causes downregulation of various immune responses in mouse and human experimental models and has been proposed as both a chromophore and a mediator of UV-induced immune suppression. In this study, the wavelength dependence from 260-340 nm for trans to cis-UCA photoisomerization in human skin was analyzed in five healthy volunteers. The resulting action spectrum demonstrated maximal cis-UCA production in the UVB spectral region of 280-310 nm. This spectral peak is red-shifted to longer wavelengths compared with the erythemal action spectrum. The cis-UCA action spectrum can be used to predict the ability of sunscreens to protect against UVR-induced cis-UCA formation and may assist in explaining discrepancies between sunscreens' abilities to protect against erythema and photoimmunosuppression.

An action spectrum (290–320 nm) for TNFα protein in human skinin vivosuggests that basal-layer epidermal DNA is the chromophore

“…2b) showed that the best match was between TNF␣ and deep basal layer CPD. We also compared our TNF␣ action spectrum with that for the photoisomerization of UCA in human skin (23), and the results are markedly different especially between 300 and 320 nm. Thus, based on human action spectroscopy in vivo, our data strongly suggest that DNA, specifically in the basal layer, is an important chromophore for TNF␣ and supports the in vitro mouse kera- tinocyte studies of Kibitel et al (11), in which T4 endonuclease V (T4N5)-enhanced CPD repair was shown to reduce TNF␣ protein production.…”

“…However, we recently concluded that these action spectra are different and that UVA is more immunosuppressive than it is erythemogenic in human skin (14). This finding suggests that other chromophores, such as UCA, also may be important, and this notion is supported by an action spectrum for the photoisomerization of trans-to cis-UCA in human skin in vivo, in which UVA had a more important role than it did for erythema (23). Some authors have suggested that cis-UCA can induce TNF␣ (30,31), but others have not supported this theory (32)(33)(34).…”

Banning children and youth under the age of 18 years from commercial tanning facilities

“…Action spectroscopy and studies with different broad-spectrum sources show that UVB is much more effective than UVA for most acute endpoints studied in human skin. This includes erythema (Anders et al, 1995;CIE 1998;Young et al, 1998), delayed pigmentation (Parrish et al, 1982), DNA photodamage and UCA photoisomerization (McLoone et al, 2005). In general, UVB is 3 to 4 orders of magnitude more effective per unit physical dose (J/cm 2 ) than UVA, but this difference depends on the specific wavelengths/wavebands being compared.…”

Solar radiation and human health

“…Essentially, two chromophores have been brought to attention: DNA [222] and trans-urocanic acid (trans-UCA) [223]. Photoisomerization of UCA, from the trans to the cis form, is thought to be a key reaction, since cis-UCA has an immunological effect and since trans-UCA is the abundant form in unexposed skin [223]. The action spectrum for photoimmunosuppression in human skin (figure 12) indicates maximal cis-UCA production in the UVB Figure 12.…”

“…The action spectrum for photoimmunosuppression in human skin (figure 12) indicates maximal cis-UCA production in the UVB Figure 12. The action spectrum for cis-UCA production in human skin [223].…”