Hyperexpression of TLR2 and TLR4 in patients with ischemic stroke in acute period of the disease
https://doi.org/10.15789/1563-0625-HOT-1971
Abstract
Pathogenesis of ischemic stroke is actively involved in the system of innate immunity. Under conditions of cerebral ischemia, a number of biologically active substances are released that interact with innate immunity receptors, in particular TLR2 and TLR4, which exacerbate inflammation in brain tissue. Identification of predictor markers at the level of the innate immunity system may foresee the clinical course of ischemic stroke and ensure timely treatment. Our objective was to study expression of TLR2 and TLR4 receptors in peripheral blood leukocytes in patients with ischemic stroke in the dynamics of the disease. 27 people were included in the study. The main group consisted of patients with ischemic stroke of varying severity (n = 19). Patients of the main group were divided into two subgroups: with an NIHSS index value of < 10 (n = 10) and > 10 (n = 9). The control group included healthy donors with no history of acute and chronic inflammatory diseases (n = 8). Peripheral blood leukocytes were used as the test material. To determine expression of the TLR2 and TLR4 genes, RT-PCR in real time was used. Surface expression of TLRs was determined by flow cytometry. A study of the TLR2 and TLR4 gene expression showed that on the 1st, 3rd and 7th day post-stroke, the TLR4 gene expression in patients was significantly increased, when compared to the control group (p < 0.01), whereas TLR2 gene expression on the 3rd day of the disease was not statistically different from the control group. A study of surface expression of receptors showed that the average TLR2 fluorescence intensity on the patients’ peripheral blood monocytes was significantly increased on the 1st and 3rd day of disease when compared to the control group. The surface expression of TLR4 on monocytes has a statistically significant increase only on day 7. Assessment of surface expression of TLRs in subgroups with different severity values by NIHSS showed that patients with a NIHSS index > 10 had a significantly higher level of surface of TLR2 expression over the observation period, while the largest difference in TLR4 expression in the subgroups was observed on the 1st day of the disease (p < 0.05). Patients with ischemic stroke showed an increase in TLR2 and TLR4 expression at the gene and protein level, compared to healthy donors. These indices can be considered possible predictors for clinical prognosis of ischemic stroke.
About the Authors
L. V. GankovskayaRussian Federation
Gankovskaya Ludmila Viktorovna - PhD, MD (Medicine), Professor, Head, Department of Immunology, Faculty of Biomedicine.
MoscowCompeting Interests: not
L. V. Stakhovskaya
Russian Federation
Stakhovskaya Ludmila Vitalevna - PhD, MD (Medicine), Professor, Head, Department of Neurology, Neurosurgery and Medical Genetics.
Moscow
Competing Interests: not
V. V. Grechenko
Russian Federation
Grechenko Vyacheslav Vladimirovich - PhD (Medicine), Associate Professor, Department of Immunology, Faculty of Biomedicine.
Moscow
Competing Interests: not
E. A. Koltsova
Russian Federation
Koltsova Evgenya Aleksandrovna - PhD (Medicine), Professor, Department of Neurology, Neurosurgery and Medical Genetics.
MoscowCompeting Interests: not
O. S. Uvarova
Russian Federation
Uvarova Olga Sergeevna - 6th year Student, Institute of Clinical Medicine.
MoscowCompeting Interests: not
M. D. Demina
Russian Federation
Demina Maria Dmitrievna - 6th year Student.
MoscowCompeting Interests: not
T. V. Gromova
Russian Federation
Gromova Tatyana Vyacheslavovna - PhD (Medicine), Associate Professor, Department of Immunology, Faculty of Biomedicine.
MoscowCompeting Interests: not
O. A. Svitich
Russian Federation
Svitich Oksana Anatolevna - PhD, MD (Medicine), Professor, Corresponding Member, Russian Academy of Sciences, Professor, Department of Immunology, Faculty of Biomedicine.
MoscowCompeting Interests: not
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4. Figure 1. Gene expression of TLR4 in the leukocyte mass of patients with ischemic stroke on the 1st, 3rd and 7th day after its development with the control group | |
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5. Figure 2. Gene expression of TLR2 in the leukocyte mass of patients with ischemic stroke on the 1st, 3rd and 7th day after its development with the control group | |
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6. Figure 3. Surface expression TLR2 on CD14+ monocytes of peripheral blood of patients with ischemic stroke in dynamic | |
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7. Figure 4. Surface expression TLR4 on CD14+ monocytes of peripheral blood of patients with ischemic stroke in dynamic | |
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8. Figure 5. Surface expression TLR2 on CD14+ monocytes of peripheral blood of patients with ischemic stroke in dynamic with different NIHSS index | |
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9. Figure 6. Surface expression TLR4 on CD14+ monocytes of peripheral blood of patients with ischemic stroke in dynamic with different NIHSS index | |
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For citations:
Gankovskaya L.V., Stakhovskaya L.V., Grechenko V.V., Koltsova E.A., Uvarova O.S., Demina M.D., Gromova T.V., Svitich O.A. Hyperexpression of TLR2 and TLR4 in patients with ischemic stroke in acute period of the disease. Medical Immunology (Russia). 2020;22(4):665-674. (In Russ.) https://doi.org/10.15789/1563-0625-HOT-1971