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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. Gankovskaya
Pirogov Russian National Research Medical University
Russian Federation

Gankovskaya Ludmila Viktorovna - PhD, MD (Medicine), Professor, Head, Department of Immunology, Faculty of Biomedicine.

Moscow

Competing Interests: not


L. V. Stakhovskaya
Pirogov Russian National Research Medical University
Russian Federation

Stakhovskaya Ludmila Vitalevna  - PhD, MD (Medicine), Professor, Head, Department of Neurology, Neurosurgery and Medical Genetics.

Moscow


Competing Interests: not


V. V. Grechenko
Pirogov Russian National Research Medical University
Russian Federation

Grechenko Vyacheslav  Vladimirovich  - PhD (Medicine), Associate Professor, Department of Immunology, Faculty of Biomedicine.

Moscow


Competing Interests: not


E. A. Koltsova
Pirogov Russian National Research Medical University
Russian Federation

Koltsova Evgenya Aleksandrovna -  PhD (Medicine), Professor, Department of Neurology, Neurosurgery and Medical Genetics.

Moscow

Competing Interests: not


O. S. Uvarova
I.M. Sechenov First Moscow State Medical University (Sechenov University), Pirogov Russian National Research Medical University
Russian Federation

Uvarova Olga Sergeevna  - 6th  year Student,  Institute of Clinical Medicine.

Moscow

Competing Interests: not


M. D. Demina
Pirogov Russian National Research Medical University
Russian Federation

Demina Maria Dmitrievna -  6th  year Student.

Moscow

Competing Interests: not


T. V. Gromova
Pirogov Russian National Research Medical University
Russian Federation

Gromova Tatyana Vyacheslavovna - PhD (Medicine), Associate Professor, Department of Immunology, Faculty of Biomedicine.

Moscow

Competing Interests: not


O. A. Svitich
Pirogov Russian National Research Medical University
Russian Federation

Svitich Oksana Anatolevna - PhD, MD (Medicine), Professor, Corresponding Member, Russian Academy of Sciences, Professor, Department of Immunology, Faculty of Biomedicine.

Moscow

Competing 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

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ISSN 1563-0625 (Print)
ISSN 2313-741X (Online)