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Open Access 01-12-2018 | Short report

The inhibitory effect of LPS on the expression of GPR81 lactate receptor in blood-brain barrier model in vitro

Authors: Elizaveta B. Boitsova, Andrey V. Morgun, Elena D. Osipova, Elena A. Pozhilenkova, Galina P. Martinova, Olga V. Frolova, Raissa Ya Olovannikova, Abolghasem Tohidpour, Yana V. Gorina, Yulia A. Panina, Alla B. Salmina

Published in: Journal of Neuroinflammation | Issue 1/2018

Abstract

Background

Lipopolysaccharide (LPS) is one of the main constituents of the cell wall of gram-negative bacteria. As an endotoxin, LPS induces neuroinflammation, which is associated with the blood-brain barrier impairment. Lactate is a metabolite with some significant physiological functions within the neurovascular unit/blood-brain barrier (BBB). Accumulation of extracellular and cerebrospinal fluid lactate is a specific feature of bacterial meningitis. However, the role of lactate production, transport, and sensing by lactate receptors GPR81 in the pathogenesis of bacterial neuroinflammation is still unknown.

Methods

In this study, we analyzed effects of LPS on the expression of GPR81 and MCT-1 and proliferation of cerebral endothelial cells in the BBB model in vitro. We used molecular profiling methods to measure the expression of GPR81, MCT-1, IL-1β, and Ki67 in the cerebral endothelium after treatment with different concentrations of LPS followed by measuring the level of extracellular lactate, transendothelial electric resistance, and permeability of the endothelial cell layer.

Results

Our findings showed that exposure to LPS results in neuroinflammatory changes associated with decreased expression of GPR81 and MCT-1 in endothelial cells, as well as overproduction of IL-1β and elevation of lactate concentrations in the extracellular space in a dose-dependent manner. LPS treatment reduced JAM tight junction protein expression in cerebral endothelial cells and altered BBB structural integrity in vitro.

Conclusion

The impairment of lactate reception and transport might contribute to the alterations of BBB structural and functional integrity caused by LPS-mediated neuroinflammation.

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Title: The inhibitory effect of LPS on the expression of GPR81 lactate receptor in blood-brain barrier model in vitro
Authors: Elizaveta B. Boitsova
Andrey V. Morgun
Elena D. Osipova
Elena A. Pozhilenkova
Galina P. Martinova
Olga V. Frolova
Raissa Ya Olovannikova
Abolghasem Tohidpour
Yana V. Gorina
Yulia A. Panina
Alla B. Salmina
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2018
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-018-1233-2

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

The inhibitory effect of LPS on the expression of GPR81 lactate receptor in blood-brain barrier model in vitro

Abstract

Background

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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