Genome-wide analysis of poly(I:C)-responsive gene expression by primary human keratinocytes with and without episomal human papillomavirus
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Judith Boer
PROVIDER: E-GEOD-21260 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Analysis of the effect of high-risk human papillomaviruses HPV16 and HPV18 in keratinocytes at gene expression level. The hypothesis tested in the present study was that HPVs inhibit the function of pathogen recognition receptors (PRRs), thereby evading the immune system. Results show that HPV-positive keratinocytes have a weaker response to poly(I:C), a synthetic double strand RNA agonist of viral PRRs, with IL1B as a central hub in a gene expression network of relative downregulation.
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Project description:The interaction between the transmembrane glycoprotein surface receptor CD40 expressed by skin keratinocytes (KCs) and its T cell-expressed ligand CD154 was suggested to exacerbate inflammatory skin diseases. However, the full spectrum of CD40-mediated effects by KCs underlying this observation is unknown. Therefore, changes in gene expression after CD40 ligation of KCs were studied by microarrays. CD40-mediated activation for 2 hours stimulated the expression of a coordinated network of immune-involved genes strongly interconnected by IL8 and TNF, while after 24 hours anti-proliferative and anti-apoptotic genes were upregulated. CD40 ligation stimulated the production of chemokines that attracted lymphocytes and myeloid cells from peripheral blood mononuclear cells (PBMCs). Thus, CD40-mediated activation of KCs resulted in a highly coordinated response of genes required for the local development and sustainment of adaptive immune responses. The importance of this process was confirmed by a study on the effects of human papilloma virus (HPV) infection to the KCâs response to CD40 ligation. HPV infection clearly attenuated the magnitude of the response to CD40 ligation and consequently the KCâs capacity to attract PBMCs. The fact that HPV attenuates CD40 signalling in KCs indicates the importance of the CD40-CD154 immune pathway in boosting cellular immunity within epithelia. Total RNA from eight 72 hours 50 IU/ml IFNgamma pre-stimulated primary undifferentiated keratinocyte cultures, four uninfected and four HPV-positive, that were either left unstimulated, or stimulated for 2 hours with IFNgamma and Control- or CD40L-expressing L-cells (mouse fibroblasts), or stimulated for 24 hours with IFNgamma and Control- or CD40L-expressing L-cells. The stimulated samples were generated in duplo. 72 samples were generated in total.
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Project description:Keratinocytes are a targeted cells for infection of human papillomaviruses (HPV). But, there are very limited information for gene regulation of human karatinocytes by HPV infection. Y-27632, a rho-kinase inhibitor, stimulates proparation of keratinocytes. We identified genes, which are regulated by a drug for karatinocyte proparation (Y-27632). mRNA profiles of primary HEKs regulated by a rho kinase inhibitor (Y-27632, Y-drug) were generated by microarray analysis using Illumina BeadChip.
2014-03-31 | E-GEOD-52515 | biostudies-arrayexpress
Project description:Previous studies have shown that normal and HPV immortalized keratinocytes are sensitive to TNF anti-proliferative effect. Conversely, HPV18-immortalized keratinocytes are resistant to the cytostatic effect mediated by this cytokine. In this study we have compared gene expression patterns in primary cultures of human foreskin epidermal keratinocytes (PHK or NHFK) and HPV16 (HF698) and HPV18(HF18Nco)-immortalized cell lines, and profile the transcriptional changes 3 and 60 hours after TNF treatment. Keywords: global expression profile, microarray, HPV, TNF
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Project description:Previous studies have shown that normal and HPV immortalized keratinocytes are sensitive to TNF anti-proliferative effect. Conversely, HPV18-immortalized keratinocytes are resistant to the cytostatic effect mediated by this cytokine. In this study we have compared gene expression patterns in primary cultures of human foreskin epidermal keratinocytes (PHK or NHFK) and HPV16 (HF698) and HPV18(HF18Nco)-immortalized cell lines, and profile the transcriptional changes 3 and 60 hours after TNF treatment. Keywords: global expression profile, microarray, HPV, TNF In order to determine the effects of HPV infection and TNF treatment on global gene expression, were performed 2 independent experiment for each cell line, including the two periods of treatment with TNF. Furthermore, were performed 2 experiments for each control plate containing the non-treated cells.
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2014-01-14 | E-GEOD-54008 | biostudies-arrayexpress
Project description:Most of the cervical cancers are caused by human papillomavirus (HPV) infection. It has been known that, in HeLa cells, HPV18 viral genome is integrated at chromosome 8q24.21 and activates transcription of proto-oncogene c-Myc. However, the mechanism of how the integrated HPV fragment exhibits transcription activation function has not been fully elucidated. In this study, we found that HPV18 transcripts themselves have an enhancer RNA-like function to activate their proximal genes including CCAT1-5L and c-Myc. We showed that the human genome-integrated HPV18 genes are activated by transcription coregulators BRD4, Mediator. The transcribed HPV18 RNAs form a liquid-like condensate at chromosome 8q24.21 locus, which in turn accumulates RNA polymerase II. Moreover, we identified uncharacterized transcript from Upstream Region of CCAT1-5L, named URC. The URC RNA is transcribed as a chimera RNA with HPV18 and is composed of 3'-untranslated region of HPV18 transcript. We found that the URC contributes to stabilization of HPV18 RNAs by supplying a poly-adenylation site for HPV18 transcript. Our findings suggest that HPV18 integration at 8q24.21 locus causes HPV18-URC chimera RNA and promotes tumorigenesis through RNA-based liquid droplet formation.
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