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

Journal of Neuroinflammation

Galina P. Martinova¹  Raissa Ya Olovannikova²  Yulia A. Panina²  Abolghasem Tohidpour²  Elena D. Osipova²  Elena A. Pozhilenkova²  Yana V. Gorina²  Olga V. Frolova²  Alla B. Salmina²  Andrey V. Morgun²  Elizaveta B. Boitsova² 

[1] Department of Children Infectious Diseases, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky;Research Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky;

关键词: Lipopolysaccharide;    Neuroinflammation;    Blood-brain barrier;    Lactate;   

DOI  :  10.1186/s12974-018-1233-2

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown