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cis ‐Urocanic Acid does not Induce the Expression of Immunosuppressive Cytokines in Murine Keratinocytes ¶ †
Author(s) -
ZakPrelich Malgorzata,
Norval Mary,
Venner Thomas J.,
Bisset Yvonne,
Walker Craig,
Rafferty Teresa S.,
Sauder Daniel N.,
McKenzie Roderick C.
Publication year - 2001
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1562/0031-8655(2001)0730238cuadni2.0.co2
Subject(s) - urocanic acid , microbiology and biotechnology , messenger rna , keratinocyte , cytokine , biology , tumor necrosis factor alpha , phorbol , interleukin 4 , immunostaining , chemistry , in vitro , immunology , signal transduction , biochemistry , protein kinase c , gene , histidine , enzyme , immunohistochemistry
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/m 2 ) 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.