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THE EFFECT OF BACTERIAL VAGINOSIS-ASSOCIATED BACTERIA ON EPITHELIAL FACTORS MEDIATING HIV TRANSMISSION
Title
THE EFFECT OF BACTERIAL VAGINOSIS-ASSOCIATED BACTERIA ON EPITHELIAL FACTORS MEDIATING HIV TRANSMISSION.
Creator
Nguyen, April, Cole, Alexander, University of Central Florida
Abstract / Description
Bacterial vaginosis (BV), a common female reproductive tract (FRT) condition characterized by an overgrowth of anaerobic species concurrent with the disappearance of commensal Lactobacilli species, is associated with a 60% increased risk of HIV-1 transmission. However, the role of the FRT epithelia in bacterial vaginosis-associated bacteria (BVAB)-augmented HIV-1 transmission is unclear. To evaluate the increased risk of HIV-1 acquisition, we treated FRT epithelia with Atopobium vaginae, a...
Show moreBacterial vaginosis (BV), a common female reproductive tract (FRT) condition characterized by an overgrowth of anaerobic species concurrent with the disappearance of commensal Lactobacilli species, is associated with a 60% increased risk of HIV-1 transmission. However, the role of the FRT epithelia in bacterial vaginosis-associated bacteria (BVAB)-augmented HIV-1 transmission is unclear. To evaluate the increased risk of HIV-1 acquisition, we treated FRT epithelia with Atopobium vaginae, a prevalent BVAB, to determine the nature of the host response to BVAB exposure. Treatment of endocervical cells with A. vaginae resulted in a 1500-fold increase in the expression of the antimicrobial peptide hBD-2, an inflammatory cytokine response, and delocalization of the tight junction protein ZO-1 from cell borders. Conditioned media (CM) from the coculture of FRT epithelia and A. vaginae also generated an inflammatory immune response and lowered the transepithelial electrical resistance in polarized endocervical monolayers. Changes in HIV-1 infection were measured in TZM-bl reporter cells, which contain a luciferase gene under the control of an HIV-1 long terminal repeat (LTR) region that is activated by the binding of Tat, an HIV-1 protein that drives viral replication. NF[kappa]B is a major host-derived transcription factor that regulates the expression of many genes involved in inflammation and the innate immune response. Interestingly, NF[kappa]B has been reported to bind Tat-activated response elements within the LTR of HIV-1, driving viral transcription. TZM-bl cells were treated with CM in the absence of HIV-1, which resulted in increased luciferase production that could be suppressed by the NF[kappa]B inhibitor TPCA-1. These data suggest that epithelially derived products from the coculture of FRT cells and A. vaginae enhance HIV-1 infection by causing cervical barrier dysfunction and increasing HIV replication efficiency through NF[kappa]B.
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Date Issued
2015
Identifier
CFH0004752, ucf:45365
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFH0004752
VARIABLE FLUID FLOW REGIMES ALTER ENDOTHELIAL ADHERENS JUNCTIONS AND TIGHT JUNCTIONS
Title
VARIABLE FLUID FLOW REGIMES ALTER ENDOTHELIAL ADHERENS JUNCTIONS AND TIGHT JUNCTIONS.
Creator
Ranadewa, Dilshan, Steward, Robert, Gou, Jihua, Mansy, Hansen, University of Central Florida
Abstract / Description
Variable blood flow regimes influence a range of cellular properties ranging from cell orientation, shape, and permeability: all of which are dependent on endothelial cell-cell junctions. In fact, cell-cell junctions have shown to be an integral part of vascular homeostasis through the endothelium by allowing intercellular signaling and passage control through tight junctions (TJs), adherens junctions (AJs), and gap junctions (GJs). It was our objective to determine the structural response of...
Show moreVariable blood flow regimes influence a range of cellular properties ranging from cell orientation, shape, and permeability: all of which are dependent on endothelial cell-cell junctions. In fact, cell-cell junctions have shown to be an integral part of vascular homeostasis through the endothelium by allowing intercellular signaling and passage control through tight junctions (TJs), adherens junctions (AJs), and gap junctions (GJs). It was our objective to determine the structural response of both AJs and TJs under steady and oscillatory flow. Human brain microvascular endothelial cells (HBMECs) were cultured in a parallel plate flow chamber and exposed to separate trails of steady and oscillatory fluid shear stress for 24 hours. Steady flow regimes consisted of a low laminar flow (LLF) of 1 dyne/cm2, and a high laminar flow (HLF) of 10 dyne/cm2 and oscillatory flow regimes consisted of low oscillatory flow (LOF) +/- 1 dyne/cm2 and high oscillatory flow (HLF) of +/- 10 dyne/cm2. We then imaged the TJs ZO-1 Claudin-5 and AJs JAM-A VE-Cadherin and subsequently analyzed their structural response as a function of pixel intensity. Our findings revealed an increase in pixel intensity between LLF and LOF along the boundary of the cells in both TJs ZO1 Claudin 5. Therefore, our results demonstrate the variable response of different cell-cell junctions under fluid shear, and for the first time, observes the difference in cell-cell junctional structure amongst steady and oscillatory flow regimes
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Date Issued
2019
Identifier
CFE0007518, ucf:52618
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0007518