Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Ex vivo effects of Tenofovir on four vaginal epithelial cell lines

ABSTRACT: In MTN-007, a phase 1, randomized, double-blinded rectal microbicide trial, we used systems genomics/proteomics to determine the effect of tenofovir 1% gel, nonoxynol-9 2% gel, placebo gel or no treatment on rectal biopsies taken at baseline, after one application or after seven daily applications (15 subjects/arm). Experiments were repeated using primary vaginal epithelial cells from four healthy women. 36 Arrays (3 primary vaginal epithelial cell lines from healthy women donors, cultured with or without 50uM or 500 uM Tenofovir for 1,4,7, or 14 days per donor cell line. A no treatment, culture media only control was included for each donor cell line and for each time point.

ORGANISM(S): Homo sapiens

SUBMITTER: Lamar Fleming

PROVIDER: E-GEOD-57026 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Mucosal effects of tenofovir 1% gel.

Hladik Florian F Burgener Adam A Ballweber Lamar L Gottardo Raphael R Vojtech Lucia L Fourati Slim S Dai James Y JY Cameron Mark J MJ Strobl Johanna J Hughes Sean M SM Hoesley Craig C Andrew Philip P Johnson Sherri S Piper Jeanna J Friend David R DR Ball T Blake TB Cranston Ross D RD Mayer Kenneth H KH McElrath M Juliana MJ McGowan Ian I

eLife 20150203

Tenofovir gel is being evaluated for vaginal and rectal pre-exposure prophylaxis against HIV transmission. Because this is a new prevention strategy, we broadly assessed its effects on the mucosa. In MTN-007, a phase-1, randomized, double-blinded rectal microbicide trial, we used systems genomics/proteomics to determine the effect of tenofovir 1% gel, nonoxynol-9 2% gel, placebo gel or no treatment on rectal biopsies (15 subjects/arm). We also treated primary vaginal epithelial cells from four h ...[more]

PMID: 25647729

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Project description:The function of human circulating proangiogenic cells (PACs) has been described extensively. However, little focus has been placed on understanding how these cells differ in their functions in the presence of microenvironments mimicking vascular inflammation. We hypothesized that exposure to proinflammatory cytokines or the oxLDL, an autoantigen abundant in advanced atherosclerotic plaques, converts PACs into immune-modulating/proinflammatory cells. Hence, we examined the effect of oxLDL and inflammatory stimuli on their phenotype by use of a functional genomics model based on secretome and whole genome transcriptome profiling. PACs obtained from culturing a PBMC fraction in angiogenic medium were primed with DC differentiation cytokines for 3 days and then exposed to proinflammatory cytokines or oxLDL for 2 days. Under these conditions, PACs converted into APCs (APCcy and APCox, respectively), expressed maturation markers CD80 and CD83, and showed an up-regulation of CD86. APCcy and APCox induced a robust T cell BrdU incorporation. Despite a similar ability to induce lymphocyte proliferation, APCcy and APCox differed for the secretory pathway and mRNA expression. Analysis of the differentially expressed genes identified 4 gene "clusters", showing reciprocal modulation in APCcy vs. APCox justifying, according to functional genomics analyses, a different putative function of the cells in antigen processing. Together, these data show that treatment with inflammatory cytokines or oxLDL converts human PAC phenotype and function into that of APCs with similar lymphocyte-activating ability but distinct maturation degree and paracrine functions. PBMC-derived PACs were committed with GM-CSF and IL-4 to a dendritic phenotype, and then exposed to proinflammatory cytokines (IL-1β and TNF-α) or to the oxidized form of LDL (oxLDL). Functional assays and whole genome gene expression profiling were performed both on PACs (n=6) and or resulting cytokine- (APCcy, n=6) and oxLDL-induced APCs (APCox, n=6). RNA was reverse transcribed, labeled, and linearly amplified, and then hybridized to HumanHT-12 v.4 Expression BeadChip microarrays. To estimate technical variability, ≈20% of the samples (n=4) were hybridized in duplicate.

Dataset Information

Ex vivo effects of Tenofovir on four vaginal epithelial cell lines

Publications

Mucosal effects of tenofovir 1% gel.

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