Molecular mechanisms linking high dose medroxyprogesterone with HIV-1 risk

PloS One
Susan C Irvin, Betsy C Herold

Abstract

Epidemiological studies suggest that medroxyprogesterone acetate (MPA) may increase the risk of HIV-1. The current studies were designed to identify potential underlying biological mechanisms. Human vaginal epithelial (VK2/E6E7), peripheral blood mononuclear (PBMC), and polarized endometrial (HEC-1-A) cells were treated with a range of concentrations of MPA (0.015-150 μg/ml) and the impact on gene expression, protein secretion, and HIV infection was evaluated. Treatment of VK2/E6E7 cells with high doses (>15 μg/ml] of MPA significantly upregulated proinflammatory cytokines, which resulted in a significant increase in HIV p24 levels secreted by latently infected U1 cells following exposure to culture supernatants harvested from MPA compared to mock-treated cells. MPA also increased syndecan expression by VK2/E6E7 cells and cells treated with 15 μg/ml of MPA bound and transferred more HIV-1 to T cells compared to mock-treated cells. Moreover, MPA treatment of epithelial cells and PBMC significantly decreased cell proliferation resulting in disruption of the epithelial barrier and decreased cytokine responses to phytohaemagglutinin, respectively. We identified several molecular mechanisms that could contribute to an association be...Continue Reading

References

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Citations

Apr 24, 2016·Journal of Obstetrics and Gynaecology Canada : JOGC = Journal D'obstétrique Et Gynécologie Du Canada : JOGC·Amanda BlackAnne Marie Whelan
Apr 24, 2016·Journal of Obstetrics and Gynaecology Canada : JOGC = Journal D'obstétrique Et Gynécologie Du Canada : JOGC·Amanda BlackAnne Marie Whelan
Jun 23, 2015·American Journal of Reproductive Immunology : AJRI·Kerry MurphyBetsy C Herold
Sep 18, 2018·The Journal of Clinical Investigation·Irina A ZalenskayaGustavo F Doncel
Jan 9, 2018·Endocrine Reviews·Janet P HapgoodZdenek Hel
Nov 5, 2015·Current Opinion in Obstetrics & Gynecology·Lauren J RalphHeidi E Jones
Jun 3, 2021·International Journal of Molecular Sciences·Anett HudákTamás Letoha

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Methods Mentioned

BETA
contraception
reverse transcription PCR
flow cytometry
ELISA
AlphaLISA
biopsies
biopsy

Software Mentioned

GraphPad Prism
FlowJo
TreeStar
GraphPad

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