Regulation of Interferon-kappa Expression in Normal and HPV-positive Human Keratinocytes

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dc.contributor.advisor Stevanovic, Stefan (Prof. Dr.)
dc.contributor.author Klein, Katrin
dc.date.accessioned 2020-06-19T09:58:10Z
dc.date.available 2020-06-19T09:58:10Z
dc.date.issued 2022-03-15
dc.identifier.uri http://hdl.handle.net/10900/101677
dc.identifier.uri http://nbn-resolving.de/urn:nbn:de:bsz:21-dspace-1016771 de_DE
dc.identifier.uri http://dx.doi.org/10.15496/publikation-43056
dc.description.abstract Type I interferons (IFNs) mediate antiviral activity, modulate immune responses and have anti-tumor activity. They impart their activities by binding to the IFN-alpha receptor on the cell surface and inducing the expression of IFN-stimulated genes (ISGs). The best-studied type I IFNs, IFN-alpha and -beta, are only expressed at very low levels in the absence of appropriate stimuli but can be strongly induced in most cell types upon activation of pattern-recognition receptors (PRRs). In contrast, IFN-kappa, another type I IFN, is expressed in a constitutive and cell type-specific manner in keratinocytes and is only weakly induced by activation of PRRs. IFN-kappa possesses activity against high risk human papillomaviruses (HR-HPV) which infect keratinocytes and IFN-kappa expression is reduced by HR-HPVs. HR-HPV represent a major health issue as they are one of the most frequently sexually transmitted infectious agents and cause virtually all cervical carcinomas, the world’s third most common cancer in women, which leads to more than 300,000 deaths per year. In the present work, regulatory mechanisms underlying the unusual pattern of IFN-kappa expression have been uncovered, using both normal and HPV16-positive human keratinocytes. It could be shown that IFN-kappa expression is mediated by the transcription factors AP-2alpha and p63, which are critically involved in keratinocyte biology and might explain the cell type-specific expression of this IFN. In addition, two signaling pathways which fine-tune IFN-kappa expression have been identified: TGF-beta1 signaling increases whereas ERK1/2 activity decreases IFN-kappa and ISG expression, both in normal and HPV16-positive keratinocytes, suggesting that IFN-kappa expression can be manipulated in pathological settings. Furthermore, increased IFN-kappa and ISG expression in HPV16-positive keratinocytes was accompanied by a decrease in viral transcription. en
dc.language.iso en de_DE
dc.publisher Universität Tübingen de_DE
dc.rights ubt-podno de_DE
dc.rights.uri http://tobias-lib.uni-tuebingen.de/doku/lic_ohne_pod.php?la=de de_DE
dc.rights.uri http://tobias-lib.uni-tuebingen.de/doku/lic_ohne_pod.php?la=en en
dc.subject.classification Humanes Papillomavirus , Interferon de_DE
dc.subject.ddc 500 de_DE
dc.subject.ddc 570 de_DE
dc.subject.other type I interferon en
dc.subject.other interferon-kappa en
dc.subject.other keratinocytes en
dc.subject.other antiviral en
dc.subject.other HPV en
dc.title Regulation of Interferon-kappa Expression in Normal and HPV-positive Human Keratinocytes en
dc.type PhDThesis de_DE
dcterms.dateAccepted 2020-05-28
utue.publikation.fachbereich Biologie de_DE
utue.publikation.fakultaet 7 Mathematisch-Naturwissenschaftliche Fakultät de_DE
utue.publikation.noppn yes de_DE

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