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. 2011:762:355-70.
doi: 10.1007/978-1-61779-185-7_26.

HIV-1-induced alterations of claudin-5 expression at the blood-brain barrier level

Ibolya E András, Michal Toborek

HIV-1-induced alterations of claudin-5 expression at the blood-brain barrier level

Ibolya E András et al. Methods Mol Biol. 2011.

Abstract

HIV-1 crosses the blood-brain barrier (BBB) early in the course of systemic infection and resides in brain macrophages and microglia. The integrity of the brain endothelium is regulated by intercellular tight junctions, which also play a critical role in HIV-1-entry into the brain. Disruption of tight junctions, including changes in claudin-5 expression, is common in HIV-1-infected patients. Recent evidence indicates that both exposure to HIV-1 and HIV-1 specific proteins, such as Tat protein, can contribute to alterations of expression and distribution of claudin-5 in brain endothelial cells and brain microvessels.

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Figures

Fig. 1
Fig. 1
Effects of Tat treatment on claudin-5 expression in brain microvascular endothe-lial cells. Confluent cultures were treated with vehicle (control) or 100 nM Tat for 24 h, and claudin-5 protein levels were detected by Western blot. In addition, selected cultures were pretreated for 15 min with U0126 (10 or 20 μM; an inhibitor of mitogen-activated protein kinase kinase1/2 [MEK1/2]), followed by a co-exposure to 100 nM Tat for 24 h (24).
Fig. 2
Fig. 2
Effects of Tat treatment on claudin-5 expression in mouse brain microvascular endothelial cells (MBMEC) as determined by immunofluorescence microscopy. Confluent primary cultures of MBMEC were derived from normal or from caveolin-1-deficient (caveolin-1−/−) mice and treated with 100 nM Tat for 24 h. In control cultures (upper left panel ), claudin-5 immunoreactivity (green staining ) was restricted to junctional areas and some punctuate staining in the cytoplasm. In addition, short branches and/or ramifications from the cell border toward the cytoplasm were observed ( arrows ). Exposure of normal MBMEC to Tat (upper right panel ) resulted in a slightly weaker junctional and cytoplasmic pattern of claudin-5 immunoreactivity. The short branching pattern of claudin-5-positive staining (arrows) was similar to that of the control cells. MBMEC isolated from caveolin-1−/− mice exhibited markedly enhanced ramification (lower left panel, arrows) of claudin-5 immunoreactivity as compared to control cells. This effect was further potentiated by Tat treatment (lower right panel, arrows; 100 nM for 24 h) resulting in a dense brush-like image of the claudin-5 immunore-activity. DAPI (blue staining) was used to visualize the nuclei.
Fig. 3
Fig. 3
Claudin-5 expression in microvessels isolated from mouse brain. Claudin-5 immunoreactivity (red staining) exhibits a linear, sharply defined pattern along the endothelial cell–cell borders and some weaker immunoreactive patterns in the cytoplasm (left panel ). DAPI (blue staining) was used to visualize the nuclei. Differential interference contrast (DIC) image was taken to visualize microvessels (middle panel). Right panel illustrates merged claudin-5 immunoreactivity and DIC images.
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