Modulation of the local expression of innate immune factors in patients with chronic endometritis and infertility
Objective. To enhance the efficiency of therapy for chronic endometritis, by modulating the local expression of innate immune factors.Dobrokhotova Yu.E., Gankovskaya L.V., Borovkova E.I., Zaidieva Z.S., Skalnaya V.S.
Subjects and methods. A study group of 43 patients with chronic endometritis and a comparison group of 15 healthy women were examined. Endometrial material was obtained by aspiration biopsy. The immunohistochemistry technique was used to estimate the number of pinopodia, receptors, infectious agents, CD138, CD20, CD8, CD4, CD56, and HLA-DRII. The investigators applied an reverse transcription-PCR assay to evaluate the expression of TLR4, TLR2, HBD1, and TNFa and ELISA to measure the level of HNP1-3. A 20-day cycle of cytokine therapy with Superlymph was performed.
Results. Epstein Bar virus was verified in 55.8% of the samples. After therapy, the number of pinopodia showed a 1.3-fold increase and the incidence of Epstein-Barr virus displayed a 2.2-fold decrease. The detection rates for CD138 and CD20 decreased by 1.6 and 1.4 times, respectively. There were 1.7- and 1.5-fold increases in the levels of T-helpers and HLA-DRII, respectively; a 1.3-fold decrease in the expression of the TLR2 gene; the expression of the TLR4, TNFα, HBD1, and HNP1-3 genes increased by 1.5-, 1.2-, 2.1-, and 1.57-fold, respectively.
Conclusion. Cytokine therapy leads to a 1.27-fold increase in the number of pinopodia;, there was a rise in the expression of TLR4 and HBD1 receptors by 5 times, TNF-a by 2.2 times, and HNP1-3 by 1.57 times. The diagnosis of active chronic endometritis was ruled out in 62.8% of patients; this condition advanced into an inactive stage in 37.2%.
Keywords
chronic endometritis
infertility
cytokine therapy
TLR2
TLR4
defensin
tumor necrosis factor
Epstein-Barr virus
human papillomavirus
References
- Ярилин А.А. Иммунология. Учебник. М.: ГЭОТАР-Медиа; 2010. 752 с. [Yarilin A.A. Immunology. Textbook. M.: GEOTAR-Media; 2010. 752 p. (in Russian)].
- Kalliolias G.D., Ivashkiv L.B. TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat. Rev. Rheumatol. 2016; 12(1): 49-62. https://dx.doi.org/10.1038/nrrheum.2015.169.
- Katila T. Post-mating inflammatory responses of the uterus. Reprod. Domest. Anim. 2012; 47(Suppl. 5): 31-41. https://dx.doi.org/10.1111/j.1439-0531.2012.02120.x.
- Bazer F.W., Wu G., Spencer T.E., Johnson G.A., Burghardt R.C., Bayless K. Novel pathways for implantation and establishment and maintenance of pregnancy in mammals. Mol. Hum. Reprod. 2010; 16(3): 135-52. https://dx.doi.org/10.1093/molehr/gap095.
- Шуршалина А.В. Хронический эндометрит как причина нарушений репродуктивной функции. Гинекология. 2012; 14(4): 16-8. [Shurshalina A.V. Chronic endometritis as a cause of impaired reproductive function. Gynecology. 2012; 14 (4): 16-8. (in Russian)]. https://dx.doi.org/10.1371/journal.pone.0214516.
- Elweza A.E., Ezz M.A., Acosta T.J., Talukder A.K., Shimizu T., Hayakawa H. et al. A proinflammatory response of bovine endometrial epithelial cells to active sperm in vitro. Mol. Reprod. Dev. 2018; 85(3): 215-26. https://dx.doi.org/10.1002/mrd.22955.
- Ezz M.A., Marey M.A., Elweza A.E., Kawai T., Heppelmann M., Pfarrer C. et al. TLR2/4 signaling pathway mediates sperm-induced inflammation in bovine endometrial epithelial cells in vitro. PLoS One. 2019; 14(4): e0214516. https://dx.doi.org/10.1371/journal.pone.0214516.
- Turner M.L., Cronin J.G., Healey G.D., Sheldon I.M. Epithelial and stromal cells of bovine endometrium have roles in innate immunity and initiate inflammatory responses to bacterial lipopeptides in vitro via Toll-like receptors TLR2, TLR1, and TLR6. Endocrinology. 2014; 155(4): 1453-65. https://dx.doi.org/10.1210/en.2013-1822.
- Park M.S., Kim J.I., Lee I., Park S., Bae J.Y., Park M.S. Towards the application of human defensins as antivirals. Biomol. Ther. (Seoul). 2018; 26(3): 242-54. https://dx.doi.org/10.4062/biomolther.2017.172.
- Cheng K., Wang X., Zhang S., Yin H. Discovery of small-molecule inhibitors of the TLR1/TLR2 complex. Angew. Chem. Int. Ed. Engl. 2012; 51(49): 12246-9. https://dx.doi.org/10.1002/anie.201204910.
- Доброхотова Ю.Э., Ганковская Л.В., Боровкова Е.И., Залесская С.А., Свитич О.А., Филина А.Б., Быстрицкая Е.П., Зайдиева З.С., Арутюнян А.М., Степанянц И.В. Совершенствование тактики ведения беременных с дисплазией шейки матки путем коррекции показателей врожденного иммунитета. Акушерство и гинекология. 2018; 12: 42-9. [Dobrokhotova Yu.E., Gankovskaya L.V., Borovkova E.I., Zalesskaya S.A., Svitich O.A., Filina A.B., Bystritskaya E.P., Zaydieva Z.S., Arutyunyan A.M., Stepanyants I.V. Improving the management of pregnant women with cervical dysplasia by correcting indicators of innate immunity. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2018; 12: 42-9. (in Russian)]. https://dx.doi.org/10.18565/aig.2018.12.42-49.
- Cronin J.G., Turner M.L., Goetze L., Bryant C.E., Sheldon I.M. Toll-like receptor 4 and MYD88-dependent signaling mechanisms of the innate immune system are essential for the response to lipopolysaccharide by epithelial and stromal cells of the bovine endometrium. Biol. Reprod. 2012; 86(2): 51-9. https://dx.doi.org/10.1095/biolreprod.111.092718.
- Lin S.C., Lo Y.C., Wu H. Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling. Nature. 2010; 465(7300): 885-90. https://dx.doi.org/10.1038/nature09121.
Received 12.04.2019
Accepted 19.04.2019
About the Authors
Dobrokhotova, Yulia E., MD, professor, head of the Department of Obstetrics and Gynecology, Medical Faculty, N.I. Pirogov Russian National Research Medical University. 117997, Russia, Moscow, Ostrovityanov str. 1/9. Tel: +74957226399. E-mail: pr.dobrohotova@mail.ru.Gankovskaya, Lydmila V., MD, professor, head of the Departament of Immunology, N.I. Pirogov Russian National Research Medical University.
117997, Russia, Moscow, Ostrovitianov str. 1/9.Tel: +74854343165. E-mail: lvgan@yandex.ru.
Borovkova, Ekaterina I., MD, associate professor, professor of the Department of Obstetrics and Gynecology N.I. Pirogov Russian National Research Medical University. 117997, Russia, Moscow, Ostrovitianov str. 1/9.Tel: +79037855793. E-mail: Katyanikitina@mail.ru.
Zaidieva, Zulya S., PhD, head of the Consultative and Diagnostic Department of the Maternity Hospital at the City Clinical Hospital Forty.
129301, Russia, Moscow, Taimyrskaya str. 6. Tel.: +79037883995. E-mail: dr.zaydieva@mail.ru
Skalnaya, Victoria S., obstetrician-gynecologist at the Consultative and Diagnostic Department of the Maternity Hospital at the City Clinical Hospital Forty.
129301, Russia, Moscow, Taimyrskaya str. 6. Tel.: +79169216414. E-mail: dworvik2010@yandex.ru.
For citation: Dobrokhotova Yu.E., Gankovskaya L.V., Borovkova E.I., Zaidieva Z.S., Skalnaya V.S. Modulation of the local expression of innate immune factors in patients with chronic endometritis and infertility. Akusherstvo i Ginekologiya/
Obstetrics and Gynecology. 2019; (5): 125-32. (in Russian)
https://dx.doi.org/10.18565/aig.2019.5.125-132
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