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• W1514311943 endingPage "224" @default.
• W1514311943 startingPage "217" @default.
• W1514311943 abstract "Abstract It is well established that solar UV radiation (UVR) suppresses cutaneous cell-mediated immunity in humans. trans-Urocanic acid (trans-UCA) is a major UVR-absorbing skin molecule that undergoes a photoisomerization to its cis-isomer following UVR exposure. Animal studies have demonstrated that cis-UCA plays a role in UVR-induced immune suppression, but the molecular mechanisms of action of cis-UCA are not fully understood. In this study, we examined changes in gene expression and synthesis of cytokines and PGE2 following UCA treatment of primary human keratinocytes. A limited microarray analysis of keratinocytes from two donors indicated that ∼400 genes were induced by solar-simulated radiation (SSR), 16 of which were also up-regulated by cis-UCA. In contrast, trans-UCA had little or no effect on gene expression. The genes up-regulated by both cis-UCA and SSR were associated with apoptosis, cell growth arrest, cytokines, and oxidative stress. Further studies using primary keratinocytes from four new donors showed that PG-endoperoxide synthase-2 was dramatically induced by cis-UCA, resulting in an enhanced secretion of PGE2 into the cell culture supernatant. cis-UCA also increased cytokine protein production such as that of TNF-α, IL-6, and IL-8 in a dose-dependent manner. SSR had the same effect as cis-UCA, but trans-UCA had no effect. In addition, activation of NF-κB and lipid peroxidation were induced by cis-UCA and SSR, but not trans-UCA, suggesting possible upstream events of the gene expression changes. The data suggest that the induction of immune suppression by cis-UCA may involve the initiation of gene transcription of immunomodulatory mediators in primary human keratinocytes." @default.
• W1514311943 created "2016-06-24" @default.
• W1514311943 creator A5013904751 @default.
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• W1514311943 date "2008-07-01" @default.
• W1514311943 modified "2023-10-18" @default.
• W1514311943 title "<i>cis</i>-Urocanic Acid Initiates Gene Transcription in Primary Human Keratinocytes" @default.
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• W1514311943 doi "https://doi.org/10.4049/jimmunol.181.1.217" @default.
• W1514311943 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18566387" @default.
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