1 Department of Pediatrics, Division Infectious Diseases, Johns Hopkins University School of Medicine, 7đôi mươi Rutl& Avenue, Baltimore, MD 21205, USA.

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HIV-1 gp1trăng tròn as well as alcohol affect blood-brain barrier permeability và bao tay fiber formation: involvement of reactive oxygen species


1 Department of Pediatrics, Division Infectious Diseases, Johns Hopkins University School of Medicine, 7trăng tròn Rutlvà Avenue, Baltimore, MD 21205, USA.

Background: HIV-1 infection commonly leads to serious HIV-1-associated neurological disorders, such as HIV-1-associated encephalopathy and dementia. In addition, alcohol is commonly used and/or abused ahy vọng AIDS patients, but it is unclear whether alcohol affects the disease progression & if it affects it, how this occurs. We hypothesized that alcohol could affect the blood-brain barrier (BBB) integrity và thus could affect the onmix and/or progression of HIV-associated neurological disorders.

Methods: Human brain microvascular endothelial cells (HBMEC) in a BBB mã sản phẩm system were pretreated with alcohol (17 và 68 mM) & subsequently coexposed with HIV-1 gp1đôi mươi. Expression of chemokine receptors CCR3, CCR5, & CXCR4 was assessed by enzyme-linked immunosorbent assay và real-time polymerase chain reaction. Changes in the permeability of the HBMEC monolayer were assessed using paracellular markers <(3)H>inulin or propidium iodide. Actin rearrangements in HBMEC were visualized by fluorescence microscopy và viability assessed using Live/Dead stain.

Results: Both gp1đôi mươi và alcohol increased the permeability of the BBB Model by up lớn 141%, without affecting HBMEC viability.

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Cotreatment with alcohol and gp1đôi mươi did not result in a significant synergistic effect. Gp1đôi mươi permeability involved chemokine receptor CCR5. Alcohol did not affect chemokine receptor expression on brain endothelial cells. Both gp1trăng tròn và alcohol reorganized the cytoskeleton and induced bít tất tay fiber formation. Inhibition of reactive sầu oxygen species (ROS) formation through NADPH blocked the effects of both gp1trăng tròn and alcohol on permeability và bức xúc fiber formation.

Conclusion: These results indicate that both HIV-1 gp1đôi mươi & alcohol induce stress fibers, causing increased permeability of the human BBB endothelium. Alcohol (68 mM)-mediated permeability increase was linked khổng lồ ROS formation. The alcohol-mediated physiological changes in the HBMEC monolayers may increase diffusion of plasma components & viral penetration across the BBB. This suggests that alcohol, especially at levels attained in heavy drinkers, can potentially contribute in a negative fashion to lớn HIV-1 neuropathogenesis.