Lipopolysaccharide-enhanced transcellular transport of HIV-1 across the blood-brain barrier is mediated by luminal microvessel IL-6 and GM-CSF View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-12

AUTHORS

Shinya Dohgu, Melissa A Fleegal-DeMotta, William A Banks

ABSTRACT

Elevated levels of cytokines/chemokines contribute to increased neuroinvasion of human immunodeficiency virus type 1 (HIV-1). Previous work showed that lipopolysaccharide (LPS), which is present in the plasma of patients with HIV-1, enhanced transcellular transport of HIV-1 across the blood-brain barrier (BBB) through the activation of p38 mitogen-activated protein kinase (MAPK) signaling in brain microvascular endothelial cells (BMECs). Here, we found that LPS (100 μg/mL, 4 hr) selectively increased interleukin (IL)-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) release from BMECs. The enhancement of HIV-1 transport induced by luminal LPS was neutralized by treatment with luminal, but not with abluminal, antibodies to IL-6 and GM-CSF without affecting paracellular permeability as measured by transendothelial electrical resistance (TEER). Luminal, but not abluminal, IL-6 or GM-CSF also increased HIV-1 transport. U0126 (MAPK kinase (MEK)1/2 inhibitor) and SB203580 (p38 MAPK inhibitor) decreased the LPS-enhanced release of IL-6 and GM-CSF. These results show that p44/42 and p38 MAPK signaling pathways mediate the LPS-enhanced release of IL-6 and GM-CSF. These cytokines, in turn, act at the luminal surface of the BMEC to enhance the transcellular transport of HIV-1 independently of actions on paracellular permeability. More... »

PAGES

167

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1742-2094-8-167

DOI

http://dx.doi.org/10.1186/1742-2094-8-167

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1041998164

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22129063


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