Development of an in vitro dual-chamber model of the female genital tract as a screening tool for epithelial toxicity

Youssef Gali, Kevin K. Ariën, Marleen Praet, Rafael Van den Bergh, Marleen Temmerman, Olivier Delezay, Guido Vanham

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

Heterosexual transmission of human immunodeficiency virus (HIV-1) is the predominant mode of infection worldwide. However, the early steps of transepithelial infection still need to be clarified. Using epithelial cells, originating from the female genital tract, and peripheral blood mononuclear cells as subepithelial target cells, an in vitro dual-chamber model of the female genital tract was developed. Remarkably, an intact layer of some cell types (HEC-1A, CaSki and Ect1) served as a protective barrier against cell-free but not against cell-associated HIV-1 that crossed the epithelial barrier through transmigration. Furthermore, dysfunctions of the epithelial layers were assessed by monitoring transepithelial electric resistance and transepithelial passage of FluoSpheres® and HIV-1 after treatment with nonoxynol-9 (N-9). Most of the functional assays showed dysfunction of the epithelial barrier at lower concentrations compared to a widely used colorimetric toxicity assay (WST-1). Finally, N-9 treatment caused a significant increase in the production of interleukin-8 (IL-8) and macrophage inflammatory protein-3α (MIP-3α) and a decrease of Secretory Leukocyte Protease Inhibitor (SLPI) and Monocyte Chemotactic Protein-1 (MCP-1) in this model. In conclusion, this model is a useful tool to (1) study HIV-1 transmission mechanisms and (2) evaluate epithelial toxicity of candidate microbicides.

Original languageEnglish
Pages (from-to)186-197
Number of pages12
JournalJournal of Virological Methods
Volume165
Issue number2
DOIs
Publication statusPublished - May 2010
Externally publishedYes

Keywords

  • Dual-chamber model
  • Epithelial toxicity
  • Female genital tract
  • HIV-1 transmission
  • Microbicides
  • Transmigration

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