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1 March 2001 cis-Urocanic Acid does not Induce the Expression of Immunosuppressive Cytokines in Murine Keratinocytes
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trans-Urocanic acid (UCA) acts as a chromophore for UV radiation in the epidermis and isomerizes to cis-UCA which then initiates some of the changes leading to UV-induced immunosuppression. The mechanism of the immunomodulation by cis-UCA is unknown at present, but one possibility is that the interaction between cis-UCA and keratinocytes causes the release of immunosuppressive cytokines locally. To test this hypothesis, PAM-212 cells, a murine keratinocyte cell line, were incubated with 0.10–100 μg/mL trans- and cis-UCA for 6 or 24 h, respectively. The expression of interleukin (IL)-10, transforming growth factor (TGF)-β and tumor necrosis factor (TNF)-α messenger RNA (mRNA) was then measured by reverse transcription-polymerase chain reaction in comparison with the mRNA for the house-keeping gene, β-actin. No change or significant induction of any of the cytokine messages occurred. However, the expression of IL-10 messenger RNA (mRNA) was induced 24 h after UVB irradiation (300 J/m2) and that of TNF-α mRNA occurred 6 h after treatment with phorbol myristate acetate. The expression of IL-10 protein was also examined by immunostaining in both PAM-212 cells and B16-F10 murine melanoma cells between 3 and 48 h after incubation with 10 and 100 μg/mL cis- and trans-UCA. No alteration was seen with either isomer at either concentration. In contrast, UVB irradiation of both cell lines resulted in a marked increase in intracellular IL-10 protein at 24 and 48 h. Therefore the upregulation of the immunosuppressive cytokines, IL-10, TNF-α and TGF-β, in keratinocytes is unlikely to be the mechanism by which cis-UCA induces immunosuppression in mice.

Malgorzata Zak-Prelich, Mary Norval, Thomas J. Venner, Yvonne Bisset, Craig Walker, Teresa S. Rafferty, Daniel N. Sauder, and Roderick C. McKenzie "cis-Urocanic Acid does not Induce the Expression of Immunosuppressive Cytokines in Murine Keratinocytes," Photochemistry and Photobiology 73(3), 238-244, (1 March 2001).<0238:CUADNI>2.0.CO;2
Received: 24 October 2000; Accepted: 1 December 2000; Published: 1 March 2001

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