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

Abstract

BackgroundLipopolysaccharide (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.MethodsIn 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.ResultsOur 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.ConclusionThe impairment of lactate reception and transport might contribute to the alterations of BBB structural and functional integrity caused by LPS-mediated neuroinflammation.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1233-2) contains supplementary material, which is available to authorized users.

Geniposide alleviates lipopolysaccharide-caused apoptosis of murine kidney podocytes by activating Ras/Raf/MEK/ERK-mediated cell autophagy

“…Lipopolysaccharide (LPS) is a compound of the cellular wall of Gram-negative bacteria [17]. Previous studies demonstrated that LPS-caused podocyte damage could be used as an in vitro cell model of proteinuria to analyze the pathogenesis of NS and testing new medicine for NS [18,19].…”

Change of reception and lactate transport by cerebral endothelium under the influence of viral and bacterial inflammation in vitro

“…Ранее нами были выявлены подобные изменения рецепции и транспорта лактата в модели бактериального воспаления гематоэнцефалического барьера in vitro [14].…”

The roles of GRP81 as a metabolic sensor and inflammatory mediator

“…The mechanism of GPR81-mediated inflammation impaired endothelial layer weakens the ability of sensing or transporting lactate, in consequence, MCT1 and GPR81 expression is reduced (Boitsova et al, 2018). In vivo, the decreased expression of GPR81 is also observed in the mouse glaucoma model.…”