The inhibitory effect of LPS on the expression of GPR81 lactate receptor in blood-brain barrier model in vitro
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-07-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-018-1233-2 |
| _version_ | 1819034830388592640 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Elizaveta B. Boitsova |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T07:39:58Z |
| format | Article |
| id | doaj.art-d7030158649045428807de78c2834dba |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-21T07:39:58Z |
| publishDate | 2018-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-d7030158649045428807de78c2834dba2022-12-21T19:11:21ZengBMCJournal of Neuroinflammation1742-20942018-07-011511710.1186/s12974-018-1233-2The inhibitory effect of LPS on the expression of GPR81 lactate receptor in blood-brain barrier model in vitroElizaveta B. Boitsova0Andrey V. Morgun1Elena D. Osipova2Elena A. Pozhilenkova3Galina P. Martinova4Olga V. Frolova5Raissa Ya Olovannikova6Abolghasem Tohidpour7Yana V. Gorina8Yulia A. Panina9Alla B. Salmina10Research Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-YasenetskyResearch Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-YasenetskyResearch Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-YasenetskyResearch Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-YasenetskyDepartment of Children Infectious Diseases, Krasnoyarsk State Medical University named after Prof. V.F. Voino-YasenetskyResearch Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-YasenetskyResearch Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-YasenetskyResearch Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-YasenetskyResearch Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-YasenetskyResearch Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-YasenetskyResearch Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-YasenetskyAbstract 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.http://link.springer.com/article/10.1186/s12974-018-1233-2LipopolysaccharideNeuroinflammationBlood-brain barrierLactate |
| spellingShingle | 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 The inhibitory effect of LPS on the expression of GPR81 lactate receptor in blood-brain barrier model in vitro Journal of Neuroinflammation Lipopolysaccharide Neuroinflammation Blood-brain barrier Lactate |
| title | The inhibitory effect of LPS on the expression of GPR81 lactate receptor in blood-brain barrier model in vitro |
| title_full | The inhibitory effect of LPS on the expression of GPR81 lactate receptor in blood-brain barrier model in vitro |
| title_fullStr | The inhibitory effect of LPS on the expression of GPR81 lactate receptor in blood-brain barrier model in vitro |
| title_full_unstemmed | The inhibitory effect of LPS on the expression of GPR81 lactate receptor in blood-brain barrier model in vitro |
| title_short | The inhibitory effect of LPS on the expression of GPR81 lactate receptor in blood-brain barrier model in vitro |
| title_sort | inhibitory effect of lps on the expression of gpr81 lactate receptor in blood brain barrier model in vitro |
| topic | Lipopolysaccharide Neuroinflammation Blood-brain barrier Lactate |
| url | http://link.springer.com/article/10.1186/s12974-018-1233-2 |
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