EXPRESSION FEATURES OF TOLL-LIKE RECEPTOR 2 AND TOLL-LIKE RECEPTOR 4 IN CHILDREN WITH ASTHMA
https://doi.org/10.15789/1563-0625-2017-4-431-440
Abstract
Currently actively discussed the role of innate immunity receptors, in particular TLRs in the immunopathogenesis of bronchial asthma (BA).
The aim of our work was to study the expression of ТLR2 and TLR4 on the nasal mucosal cells and peripheral blood leukocytes of patients with BA of different severity.
The study included 40 children with asthma (3-12 years) and 10 healthy children. Methods: real-time PCR, flow cytometry and multiplex immunofluorescence analysis evaluated the levels of pro and anti-inflammatory cytokines (IL-1β, IL-1ra, IL-6, IL-8, IL-10, TNFα) in nasal swabs.
The result of the study hyperactivation of the factors of innate immunity at the level of the mucosal of the nasal cavity in patients with asthma, manifested by increased gene expression of TLR2, TLR4, and production of proinflammatory as well as anti-inflammatory cytokines. Correlation between cytokine levels and the severity of asthma. In the peripheral blood identified a significant increase in the expression of TLR2 and TLR4 on circulating CD14+ monocytes in children with BA.
Thus, the increase of gene expression of TLRs mucosa of the nasal cavity, increase surface expression of TLR2 and TLR4 on circulating monocytes of patients with bronchial asthma compared to healthy children. The revealed changes indicate the involvement of the system of TLRs in the immunopathogenesis of bronchial asthma. In the future, TLRs can be used as markers to predict the course of ad and possible therapeutic targets.
About the Authors
L. V. GankovskayaRussian Federation
PhD, MD (Medicine), Professor, Head, Department of Immunology, Medicobiologic Faculty.
MoscowL. S. Namazova-Baranova
Russian Federation
PhD, MD (Medicine), Professor, Full Member, Russian Academy of Sciences, Head, Department of Pediatrics No. 1, RN N. Pirogov RMU; Deputy-director on Science, National Scientific and Practical Center of Children's Health.
Moscow
M. V. Khoreva
Russian Federation
PhD, MD (Medicine), Professor, Department of Immunology, Medicobiologic Faculty.
Moscow
B. G. Bragvadze
Russian Federation
Bragvadze Bella G. - Postgraduate Student, Department of Immunology, Medicobiologic Faculty.
117513, Moscow, Ostrovityanova str., 1, bldg 9. Phone: 7 (925) 302-01-63
A. D. Ogurtsova
Russian Federation
Postgraduate Student, Department of Immunology, Medicobiologic Faculty.
Moscow
A. A. Alekseeva
Russian Federation
PhD (Medicine), Department of Pediatrics No. 1, RN N. Pirogov RMU; Head of the Department of rehabilitation of children with allergic diseases and respiratory diseases, NSPCCH.
Moscow
V. А. Gankovskii
Russian Federation
PhD (Medicine), The ENT specialist of the Department of rehabilitation treatment of children with diseases of ENT organs and oral and maxillofacial region.
Moscow
O. А. Svitich
Russian Federation
PhD, MD (Medicine), Corresponding Member, Russian Academy of Sciences, Assistant Professor, Department of Immunology, Medicobiologic Faculty.
Moscow
References
1. Богомильский М.Р., Свитич О.А., Ганковский В.А., Рахманова И.В. Особенности врожденного иммунитета у здоровых детей и у детей с гипертрофией аденоидных вегетаций // Вестник РГМУ, 2015. № 4. С. 24-27. [Bogomilsky M.R., Svitich O.A., Gankovskiy V.A., Rakhmanova I.V. Innate immunity features in healthy children and in children with adenoid hypertrophy. Vestnik RGMU = Bulletin of Russian State Medical University, 2015, no. 4, pp. 24-27. (In Russ.)]
2. Зайцева М.А., Брагвадзе Б.Г., Свитич О.А., Ганковская Л.В.. Ассоциация полиморфных маркеров, локализованных в 5’-нетранслируемой области гена DEFB1 с бронхиальной астмой у детей // Вестник РГМУ, 2016. № 4. С. 43-47. [Zаitsеvа М.А., Bragvadze B.G., Svitich O.A., Gankovskaya L.V. Analysis of TLRs genes expression and defb1 polymorphisms association in children with bronchial asthma. Vestnik RGMU = Bulletin of Russian State Medical University, 2016, no. 4, pp. 43-47. (In Russ.)]
3. Ковальчук Л.В., Ганковская Л.В., Мешкова Р.Я. Клиническая иммунология и аллергология с основами общей иммунологии. M.: ГЕОТАР-Медиа, 2011. C. 148-165. [Kovalchuk L.V., Gankovskaya L.V., Meshkova R. Ya. Clinical immunology and allergology with the basics of general immunology]. Moscow: GEOTAR-Media, 2011, pp. 148-165. (In Russ.)]
4. Ковальчук Л.В., Свитич О.А., Ганковская Л.В., Мироншиченкова А.М., Ганковский В.А. Роль TOLLподобных рецепторов в патогенезе инфекционных заболеваний человека // Курский научно-практический вестник «Человек и его здоровье», 2012. № 2. С. 147-153. [Kovalchuk L.V., Svitich O.A., Gankovskaya L.V., Mironchenko M.A., Gankovskaya V.A. The role of TOLL-like receptors in the pathogenesis of human infectious diseases. Kurskiy nauchno-prakticheskiy vestnik «Chelovek i ego zdorovye» = Kurskiy Scientifically-Practical Bulletin «Person and His Health», 2012, no. 2, pp. 147-153. (In Russ.)]
5. Ковальчук Л.В., Хорева М.В., Никонова А.С. Распознающие рецепторы врожденного иммунитета (NLR, RLR И CLR) // Журнал микробиологии, эпидемиологии и иммунобиологии, 2011. № 1. С. 93-100. [Kovalchuk L.V., Khoreva, M.V., Nikonova A.S. Recognition receptors of innate immunity (NLR, RLR and CLR). Zhurnal mikrobiologii, epidemiologii i immunobiologii = Journal of Microbiology, Epidemiology and Immunobiology, 2011, no. 1, pp. 93-100. (In Russ.)]
6. Чучалин А.Г., Оспельникова Т.П., Осипова Г.Л. Роль респираторных инфекций в обострениях бронхиальной астмы // Пульмонология, 2007. № 5. С. 32-34. [Chuchalin A.G., Ospelnikova T.P., Osipova G.L. The role of respiratory infections in exacerbations of bronchial asthma. Pul`monologiya = Pulmonology, 2007, no. 5, pp. 32-34. (In Russ.)]
7. Bezemer G.F., Sagar S., van Bergenhenegouwen J., Georgiou N.A., Garssen J., Kraneveld A.D., Folkerts G. Dual role of Toll-like receptors in asthma and chronic obstructive pulmonary disease. Pharmacol. Rev., 2012, no. 64, pp. 337-358.
8. Cirillo I., Marseglia G., Klersy C., Ciprandi G. Allergic patients have more numerous and prolonged respiratory infections than nonallergic subjects. Allergy, 2007, Vol. 62, no. 9, pp. 1087-1090.
9. Crespo-Lessmann A., Mateus E., Vidal S., Ramos-Barbón D., Torrejón M., Giner J., Soto L., Juárez C., Plaza V. Expression of toll-like receptors 2 and 4 in subjects with asthma by total serum IgE level. Respir. Res., 2016, no. 17, p.41.
10. Diogenes S. Ferreira, Raquel Annoni, Luiz F.F. Silva, Monique Buttignol, Angela B.G. Santos, Maria C.R. Medeiros, Luciana N.S. Andrade, Ching Y. Yick, Peter J. Sterk, Jorge L.M. Sampaio, Marisa Dolhnikoff, Sally E. Wenzel, Thais Mauad. Toll-like receptors, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma. Clin. Exp. Allergy, 2012, Vol. 42, no. 10, pp. 1459-1471.
11. Gankovskii V., Svitich O., Gankovskaya L., Alekseeva A., Zaiceva M., Bragvadze B., Namazova-Baranova L. Association between a functional single nucleotide polymorphism in the DEFB-1 gene and risk of child asthma. Community, Diversity, Vitality, 2016, p. 44.
12. Khoreva M.V., Gankovskaya L.V., Latisheva T.V. Expression and functional analysis of toll-like receptor 4 on peripheral blood monocytes in asthmatic patients. Proceedings Allergy & Immunophysiology: Innovate Technologies, 2016, pp. 43-51.
13. Pace E., Di Sano C., Ferraro M., Bruno A., Caputo V., Gallina S., Gjomarkaj M. Budesonide increases TLR4 and TLR2 expression in Treg lymphocytes of allergic asthmatics. Pulm. Pharmacol. Ther., 2015, no. 32, pp. 93-100.
14. Svitich O., Gankovskaya L., Namazova-Baranova L., Gankovskii V., Zaiceva M., Alekseeva A., Bragvadze B. Association of SNPS in DEFB1 gene and HBD-1 expression with bronchial asthma. Allergy, 2016, Vol. 71, no. S102, p. 280.
15. Tashiro H., Takahashi K., Hayashi S., Kato G., Kurata K., Kimura S., Sueoka-Aragane N. Interleukin-33 from Monocytes Recruited to the Lung Contributes to House Dust Mite-Induced Airway Inflammation in a Mouse Model. PLoS One, 2016, no. 11, pp. 1-16.
16. Wark Р., Johnston S. Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. The Journal of Experimental Medicine, 2005, no. 6, pp. 937-947.
Review
For citations:
Gankovskaya L.V., Namazova-Baranova L.S., Khoreva M.V., Bragvadze B.G., Ogurtsova A.D., Alekseeva A.A., Gankovskii V.А., Svitich O.А. EXPRESSION FEATURES OF TOLL-LIKE RECEPTOR 2 AND TOLL-LIKE RECEPTOR 4 IN CHILDREN WITH ASTHMA. Medical Immunology (Russia). 2017;19(4):431-440. (In Russ.) https://doi.org/10.15789/1563-0625-2017-4-431-440