UVB induces IL-12 transcription in human keratinocytes in vivo and in vitro.
Human epidermal cells produce a wide range of cytokines, including those characteristic of Th2-like responses such as interleukin (IL)-4 and IL-10. As well, keratinocytes have recently been shown to produce Th1-like cytokines such as IL-12. Exposure to UVB has profound effects on the skin and systemic immune system, which is in part mediated by secretion of tumor necrosis factor (TNF)-alpha by epidermal cells. Because IL-12 induces production of TNF-alpha by certain cells of the immune system, we sought to determine whether UVB is an inducer of IL-12 gene expression in epidermal cells. Human epidermal cells were exposed to UVB radiation in vivo, isolated by suction blister technique and trypsinization and transcription of the IL-12 p35 and p40 chains was examined by RT-PCR. We found the p35 chain of IL-12 to be constitutively expressed and the p40 chain inducible by UVB irradiation. Because epidermis consists of a heterogenous cell population with distinct cytokine repertoires, we sought to determine the cellular source of the IL-12 message after UVB exposure. After depleting UVB-exposed epidermal cells for DR+ cells, no reduction in the IL-12 activity was detected, suggesting that keratinocytes are a source of IL-12 transcripts in UVB-exposed human epidermis. This was supported by the up-regulation of IL-12 p40 transcripts in UV-irradiated cultured keratinocytes that were devoid of DR+ cells. Up-regulation of IL-12 p40 gene expression by UVB as demonstrated here, taken together with the finding that keratinocytes also up-regulate IL-10 transcription, suggests that there is a complex interplay between Th1- and Th2-like epidermis-derived cytokines following exposure to UVB.
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Dermatology Branch, National Cancer Institute, Bethesda, MD 20892-1908, USA.
Mahanty
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Blauvelt
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Katz
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D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000737:chemistry / Q000235:genetics*; D015603:Keratinocytes / Q000378:metabolism* / Q000528:radiation effects*; D008969:Molecular Sequence Data; D018462:Photobiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000528:radiation effects; D014158:Transcription, Genetic / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*; D015854:Up-Regulation / Q000528:radiation effects
D017931:DNA Primers; D012333:RNA, Messenger; D018664:Interleukin-12