Effects of low concentrations of cis- and trans-urocanic acid on cytokine elaboration by keratinocytes.
The urocanic acid cis isomer (cis-UCA) is a possible cutaneous photoreceptor for the immunomodulatory phenomena that follow ultraviolet B irradiation. Several experiments in animals show an inhibitory action of cis-UCA on cellular immunity. However, the action of cis-UCA on the synthesis of cytokines in keratinocytes remains unknown. Long-term cultures of normal human keratiocytes were prepared in a serum-free medium, and stimulated with 1 microgram/ml of phorbol 12-myristate 13-acetate (TPA) and UCA or UVB-UCA (10-100 micrograms/ml). Synthesis of the following cytokines was measured using ELISA and Northern blot techniques: TNF-alpha, IL-1 alpha, IL-1 beta, IL-6, IL-8 and TGF-beta 1. TPA increased TNF-alpha protein levels in culture supernatants. No changes in Il-1 alpha and IL-1 beta protein levels were detected in basal culture supernatant after TPA stimulus. TPA augmented RNA expression for TNF-alpha, IL-1 alpha, IL-1 beta and TGF-beta 1. UCA isomers did not induce cytokine changes in protein synthesis. Expression of IL-1 alpha and IL-1 beta genes was increased after exposure to 100 micrograms/ml UVB-UCA (70 micrograms/ml cis-UCA). A slight increase in TNF-alpha RNA expression was detected when the dose of UVB-UCA reached 100 micrograms/ml. No effects on cytokine synthesis were found after UCA stimulus. These results suggest that low doses of cis-UCA do not effect cytokine synthesis by keratinocytes.
Redondo
P
P
Department of Dermatology, University Clinic of Navarra, School of Medicine, Pamplona, Spain.
García-Foncillas
J
J
Cuevillas
F
F
España
A
A
Quintanilla
E
E
D001940:Breast; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D007700:Kinetics; D012867:Skin / Q000166:cytology*; D013237:Stereoisomerism; D013755:Tetradecanoylphorbol Acetate; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014466:Ultraviolet Rays; D014560:Urocanic Acid / Q000494:pharmacology*
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D014560:Urocanic Acid; D013755:Tetradecanoylphorbol Acetate