Cytokine-regulating activity of anti-virus preparation CelAgripus in Burkitt's lym-phoma stable B-cell lines

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Abstract

Introduction. Cytokines activated in response to immunosuppressive viral infections can directly or indirectly affect the neoplastic transformation of B cells. In this study, we studied a new substance designed to produce the antiviral drug CelAgrip (CA, CelAgripus), which exhibits interferon (IFN) and cytokine-inducing activity and, apparently, can be used as an activator of antiviral immunity.

Purpose - is to evaluate the cytokine-regulating effect of CA in Burkitt's lymphoma (LB) cell lines latently infected with the Epstein-Barr virus (EBV).

Objectives: to study the CA-induced expression of the cytokine genes IL-ip, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, IL-18, IFN-a, IFN -Y, IFN-p, IFN-A1, IFN-A2, IFN-A3, TNF-a in normal and EBV transformed LB cells.

Material and methods. Cell line: the human embryo fibroblasts (HEF), Namalva, Daudi, Raji, P3HR-1. Preparations: CA, gossypol-acetic acid (GAA), sodium carboxymethyl cellulose (Na-CMC). Methods: RT-PCR and methods for assessing cytotoxicity (MTT and Scepter 2.0 Merck cell counter).

Results. The effect of the CA preparation on the expression of IFN-Л, IL-1p, IL-6, IL-8 and IL-10 genes was revealed. Discussion. We observed the activation of gene expression of IFN-A, IL-1P, IL-6, IL-8 and suppression of IL-10 gene activity when treatment CA of LB cells.

Conclusion. The substance CA has new effects on the activation of the expression of a number of key cytokine genes in stable Burkitt lymphoma cell lines.

About the authors

A. N. Narovlyansky

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F.Gamaleya

Author for correspondence.
Email: narovl@yandex.ru
ORCID iD: 0000-0003-0601-7148

Alexander N. Narovlyansky - DBS, Chief Researcher of the Cytokine Laboratory.

Moscow, 123098.

Russian Federation

M. V. Mezentseva

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F.Gamaleya

Email: fake@neicon.ru
ORCID iD: 0000-0001-7346-5536

Moscow, 123098.

Russian Federation

I. A. Suetina

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F.Gamaleya

Email: fake@neicon.ru
ORCID iD: 0000-0003-2878-0590

Moscow, 123098.

Russian Federation

L. I. Russu

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F.Gamaleya

Email: fake@neicon.ru
ORCID iD: 0000-0001-6353-9917

Moscow, 123098.

Russian Federation

A. M. Ivanova

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F.Gamaleya

Email: fake@neicon.ru
ORCID iD: 0000-0002-6008-7967

Moscow, 123098.

Russian Federation

V. V. Poloskov

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F.Gamaleya

Email: fake@neicon.ru
ORCID iD: 0000-0003-0001-2493

Moscow, 123098.

Russian Federation

A. V. Izmest'eva

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F.Gamaleya

Email: fake@neicon.ru
ORCID iD: 0000-0002-0035-324X

Moscow, 123098.

Russian Federation

T. P. Ospelnikova

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F.Gamaleya

Email: fake@neicon.ru
ORCID iD: 0000-0002-1580-6096

Moscow, 123098.

Russian Federation

A. A. Sarymsakov

Institute of Polymer Chemystry and Physics Uzbek Academy of Sciences

Email: fake@neicon.ru
ORCID iD: 0000-0003-4562-7280

Tashkent, 100128.

Uzbekistan

F. I. Ershov

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F.Gamaleya

Email: fake@neicon.ru
ORCID iD: 0000-0002-4780-7560

Moscow, 123098.

Russian Federation

References

  1. Epstein M.A. Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet. 1964; 1(7335): 702-3. Doi: https://doi.org/10.1016/s0140-6736(64)91524-7
  2. Ndede I., Mining S.K., Patel K., Wanjala F.M., Chumba D., Tenge C. Cytokines associated with Burkitt’s lymphoma in western Kenya. BMC Res. Notes. 2017; 10(1): 519. Doi: https://doi.org/10.1186/s13104-017-2841-0
  3. Miyauchi K., Urano E., Yoshiyama H., Komano J. Cytokine signatures of transformed B cells with distinct Epstein-Barr virus latencies as a potential diagnostic tool for B cell lymphoma. Cancer Sci. 2011; 102(6): 1236-41. Doi: https://doi.org/104111/j.1349-7006.2011.01924.x
  4. Liu Y., de Waal Malefyt R., Briere F., Parham C., Bridon J.M., Banchereau J., et al. The EBV IL-10 homologue is a selective agonist with impaired binding to the IL-10 receptor. J. Immunol. 1997; 158(2): 604-13.
  5. Jog N.R., Chakravarty E.F., Guthridge J.M., Judith A., James J.A. Epstein Barr Virus Interleukin 10 Suppresses Antiinflammatory Phenotype in Human Monocytes. Front. Immunol. 2018; 9: 2198. Doi: https://doi.org/10.3389/fimmu.2018.02198
  6. Ершов Ф.И., Киселев О.И. Интерфероны и их индукторы (от молекул до лекарств). М.: ГЭОТАР-Медиа; 2005.
  7. Ершов Ф.И., Наровлянский А.Н. Интерфероны и индукторы интерферонов. В кн.: Хаитов Р.М., Атауллаханов Р.И., Шульженко А.Е., ред. Иммунотерапия: руководство для врачей. М.: ГЭОТАР-Медиа; 2018: 123-47.
  8. Атаханов А.А., Сарымсаков А.А., Рашидова С.Ш. Наносистемы целлюлозы и серебра: синтез, структура и свойства. Ташкент; 2016.
  9. Klein G., Dombos L., Gothoskar B. Sensitivity of Epstein-Barr virus (EBV) producer and non-producer human lyphoblastoid cell lines to superinfection with EBV. Int. J. Cancer. 1972; 10(1): 44-57. Doi: https://doi.org/10.1002/ijc.2910100108
  10. Klein E., Klein G., Nadkarni J.S., Nadkarni J.J., Wigzell H., Clifford P. Surface IgM kappa specificity on a Burkitt lymphoma cell in vivo and in derived cultured lines. Cancer Res. 1968; 28(7): 1300-10.
  11. Pulvertaft R.J.V., Cantab M.D. Cytology of Burkitt’s tumour (African lymphoma). Lancet. 1964; 283(7327): 238-40. Doi: https://doi.org/10.1016/S0140-6736(64)92345-1
  12. Hinuma Y., Konn M., Yamaguchi J., Grace J.T. Replication of Herpes-Type Virus in a Burkitt Lymphoma Cell Line. J. Virol. 1967; 1(6): 1045-51.
  13. Хабриев Р.У., ред. Руководство по экспериментальному (доклиническому) изучению новых фармакологических веществ. М.: Медицина; 2005.
  14. PrimerBank. PCR Primers for Gene Expression Detection and Quantification. Available at: https://pga.mgh.harvard.edu/primerbank_
  15. Платэ Н.А., Васильев А.Е. Физиологически активные полимеры. М.: Химия; 1986.
  16. Pickering L.A., Kronenberg L.H., Stewart W.E. Spontaneous production of human interferon. Proc. Natl. Acad. Sci. U.S.A. 1980; 77(10): 5938-42. Doi: https://doi.org/10.1073/pnas.77.10.5938
  17. Mostafavi S., Yoshida H., Moodley D., LeBoite H., Rothamel K., Raj T., et al. Parsing the interferon transcriptional network and its disease associations. Cell. 2016; 164(3): 564-78. Doi: https://doi.org/10.1016/j.cell.2015.12.032
  18. Sarhan J., Liu B.C., Muendlein H.I., Weindel C.G., Irina Smirnova I., Tang A.Y., et al. Constitutive interferon signaling maintains critical threshold of MLKL expression to license necroptosis. Cell Death Differ. 2019; 26(2): 332-47. Doi: https://doi.org/10.1038/s41418-018-0122-7
  19. Abt M.C., Osborne L.C., Monticelli L.A., Doering T.A., Alenghat T., Sonnenberg G.F., et al. Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity. 2012; 37(1): 158-70. Doi: https://doi.org/10.1016/j.immuni.2012.04.011
  20. van Kooten C., Rensink I., Aarden L., van Oers R. Cytokines and Intracellular Signals Involved in the Regulation of B-CLL Proliferation. Leuk. Lymphoma. 1993; 12(1-2): 27-33. Doi: https://doi.org/10.3109/10428199309059568
  21. Purdue M.P., Lan Q., Kricker A., Grulich A.E., Vajdic C.M., Turner J. Polymorphisms in immune function genes and risk of non-Hodgkin lymphoma: findings from the New South Wales non-Hodgkin Lymphoma Study. Carcinogenesis. 2007; 28(3): 704-12. Doi: https://doi.org/10.1093/carcin/bgl200
  22. Warzocha K., Salles G., Bienvenu J., Bastion Y., Dumontet C., Renard N., et al. Tumor necrosis factor ligand-receptor system can predict treatment outcome in lymphoma patients. J. Clin. Oncol. 1997; 15(2): 499-508. Doi: https://doi.org/10.1200/JCO.1997.15z2.499
  23. Tian T., Wang M., Ma D. TNF-a, a good or bad factor in hematological diseases? Stem Cell Investig. 2014; 1: 12. Doi: https://doi.org/10.3978/j.issn.2306-9759.2014.04.02
  24. Gardella S., Andrei C., Costigliolo S., Poggi A., Zocchi M.R., Rubartelli A. Interleukin-18 synthesis and secretion by dendritic cells are modulated by interaction with antigen-specific T-cells. J. Leukoc. Biol. 1999; 66(2): 237-41.
  25. Lorey S.L., Huang Y.C., Sharma V. Constitutive expression of Interleukin-18 and Interleukin-18 receptor mRNA in tumour derived human B-cell lines. Clin. Exp. Immunol. 2004; 136(3): 456-62. Doi: https://doi.org/10.1111/j.1365-2249.2004.02465.x
  26. IL1B interleukin 1 beta (Homo sapiens (human); Gene ID: 3553. Available at: https://www.ncbi.nlm.nih.gov/gene/3553_
  27. IL6 interleukin 6 Homo sapiens (human); Gene ID: 3569. Available at: https://www.ncbi.nlm.nih.gov/gene/3569
  28. Anestakis D., Petanidis S., Kalyvas S., Nday C.M., Tsave O., Kioseoglou E., et al. Mechanisms and Applications of Interleukins in Cancer Immunotherapy. Int. J. Mol. Sci. 2015; 16(1): 1691-710. Doi: https://doi.org/10.3390/ijms16011691
  29. Akdis M., Aab A., Altunbulakli C., Azkur K. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor P, and TNF-a: Receptors, functions, and roles in diseases. JACI. 2016; 138(4): 984-1010. Doi: https://doi.org/10.1016/jjaci.2016.06.033
  30. Waugh D.J., Wilson C. The interleukin-8 pathway in cancer. Clin. Cancer Res. 2008; 14(21): 6735-41. Doi: https://doi.org/10.1158/1078-0432.ccr-07-4843
  31. Sunaga N., Kaira K., Tomizawa Y., Shimizu K., Imai H., Takahashi G., et al. Clinicopathological and prognostic significance of interleukin-8 expression and its relationship to KRAS mutation in lung adenocarcinoma. Br. J. Cancer. 2014; 110(8): 2047-53. Doi: https://doi.org/10.1038/bjc.2014.110
  32. Lee H.L., Eom H.S., Yun T., Kim H.J., Park W.S., Nam B.H., et al. Serum and urine levels of interleukin-8 in patients with non-Hodgkin’s lymphoma. Cytokine. 2008; 43(1): 71-5. Doi: https://doi.org/10.1016/j.cyto.2008.04.004
  33. Miyata-Takata T., Takata K., Toji T., Goto N., Kasahara S., Takahashi T., et al. Elevation of serum interleukins 8, 4, and 1p levels in patients with gastrointestinal low-grade B-cell lymphoma. Sci. Rep. 2015; 5:18434. Doi: https://doi.org/10.1038/srep18434
  34. Wikipedia, The Free Encyclopedia. IL10. Available at: https://en.wikipedia.org/wiki/Interleukin_10
  35. Sabat R., Grutz G., Warszawska K., Kirsch S., Witte E., Wolk K., et al. Biology of interleukin-10. Cytokine Growth Factor Rev. 2010; 21(5): 331-44. Doi: https://doi.org/10.1016/j.cytogfr.2010.09.002
  36. Berti F.C.B., de Oliveira K.B. IL-10 in cancer: Just a classical im-munosuppressive factor or also an immunostimulating one? AIMS AllergyImmunol. 2018; 2(2): 88-97. Doi: https://doi.org/10.3934/Allergy.2018.2.88

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Copyright (c) 2019 Narovlyansky A.N., Mezentseva M.V., Suetina I.A., Russu L.I., Ivanova A.M., Poloskov V.V., Izmest'eva A.V., Ospelnikova T.P., Sarymsakov A.A., Ershov F.I.

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