Binase induces pro-inflammatory immune response of macrophages



Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Biopharmaceutical agents, especially proteins, may possess a broad spectrum of immunological effects. Cytotoxic ribonucleases, such as binase - RNase of Bacillus pumilus, have a significant potential as anticancer therapeutical agents. However without comprehensive analysis of immune system reactions on the proteins, the practical utility of them is complicated. Using the flow cytometry we estimated qualitative and quantitative changes in IL-6, IL-10, МСР-1 and TNF-acytokines synthesis by peripheral macrophages of mice under the influence of binase and RNAse A. We established that binase in concentration 100 and 300 jg/ml, in contrast to RNase A, is able to activate pro-inflammatory response of macrophages, inducing increase of IL-6, МСР-1 andTNF-a cytokines level in cultural media. Treatment with RNases does not enhance the antiinflammatory cytokime IL-10 synthesis. Obtained data lead as to the assumption, that binase capability to activate pro-inflammatory response of macrophages will intensify its antitumor effects in vivo.

Full Text

Restricted Access

About the authors

A. P Lozhkin

Kazan (Volga Region) Federal University

P. V Zelenikhin

Kazan (Volga Region) Federal University

A. V Makeeva

Kazan (Volga Region) Federal University

E. A Sokolova

Kazan (Volga Region) Federal University

O. N Ilinskaya

Kazan (Volga Region) Federal University

References

  1. Tovey M.G., Lallemand C. Immunogenicity and other problems associated with the use of biopharmaceuticals. Ther.Adv.Drug.Saf. 2011; 2: 113-28.
  2. Weiner H.L., Cohen J.A. Treatment of multiple sclerosis with cyclophosphamide: critical review of clinical and immunologic effects. Mult. Scler. 2002; 8: 142-54.
  3. Weinblatt M.E. Methotrexate in rheumatoid arthritis: a quarter century of development. Trans. Am. Clin. Climatol. Assoc. 2013; 124: 16-25.
  4. Seggewiss R., Lore K., Greiner E. et al. Imatinib inhibits T-cell receptor-mediated T-cell proliferation and activation in a dose-dependent manner. Blood. 2005; 105: 2473-9.
  5. Zagozdzon R., Golab J., Stoklosa T. et al.Effective chemo-immunotherapy of L1210 leukemia invivousing interleukin-12 combined with doxorubicin but not with cyclophosphamide, paclitaxel or cisplatin. Int. J. Cancer. 1998; 77: 720-7.
  6. Plate J.M., Plate A.E., Shott S.et al.Effect of gemcitabine on immune cells insubjects with adenocarcinoma of the pancreas. Cancer Immunol. Immunother. 2005; 54: 915-25.
  7. Tanaka F., Yamaguchi H., Ohta M. et al. Intratumoral injection of dendritic cells after treatment of anticancer drugs induces tumor-specific antitumor effect in vivo. Int. J.Cancer. 2002; 101: 265-9.
  8. Makarov A.A., Kolchinsky A., Ilinskaya O.N. Binase and other microbial RNases as potential anticancer agents. Bioessays 2008; 30: 781-90.
  9. Rutkoski T.J., Raines R.T. Evasion of ribonuclease inhibitor as a determinant of ribonuclease cytotoxicity. Curr. Pharm. Biotechnol. 2008; 9: 185-9.
  10. Matousek J. Ribonucleases and their antitumor activity. Comp. Biochem. Physiol. C. Toxicol. Pharmacol. 2001; 129: 175-91.
  11. Ilinskaya O.N., Zelenikhin P.V., Petrushanko I.Y. et al. Binase induces apoptosis of transformed myeloid cells and does not induce T-cell immune response. Biochem. Biophys. Res. Commun. 2007; 361: 1000-5.
  12. Ilinskaya O.N., Ivanchenko O.B., Karamova N.S. et al. SOS-inducing ability of native and mutant microbial ribonucleases. Mutat. Res. 1996; 354: 203-9.
  13. Deshmane S.L., Kremlev S., Amini S. et al. Monocyte chemoattractant protein-1 (MCP-1): an overview. J. Interferon. CytokineRes. 2009; 29: 313-26.
  14. Scholz D., Ito W., Fleming I. et al. Ultrastructure and molecular histology of rabbit hind-limb collateral artery growth (arteriogenesis). Virchows Arch. 2000; 436: 257-70.
  15. Polverini P.J., Cotran P.S., Gimbrone M.A. et al. Activated macrophages induce vascular proliferation. Nature 1977; 269: 804-6.
  16. Biswas P., Delfanti F., Bernasconi S. et al. Interleukin-6 induces monocyte chemotactic protein-1 in peripheral blood mononuclear cells and in the U937cell line. Blood 1998; 91: 258-65.
  17. Dethlefsen C., Hojfeldt G., Hojman P. The role of intratumoral and systemic IL-6 in breast cancer. Breast Cancer Res. Treat. 2013; 138: 657-64.
  18. van Horssen R., Ten Hagen T.L., Eggermont A.M. TNF-alpha in cancer treatment: molecular insights, antitumor effects, and clinical utility. Oncologist 2006; 11: 397-408.
  19. Kamimura D., Ishihara K., Hirano T. IL-6signal transduction and its physiological roles: the signal orchestration model. Rev. Physiol. Biochem. Pharmacol. 2003; 149: 1-38.
  20. Mitkevich V.A., Kretova O.V., Petrushanko I.Y. et al. Ribonuclease binase apoptotic signature in leukemic Kasumi-1 cells. Biochimie. 2013; 95: 1344-9.
  21. Scott M.J., Hoth J.J., Turina M. Interleukin-10 suppresses natural killer cell but not natural killer T cell activation during bacterial infection. Cytokine 2006; 33: 79-86.
  22. Wu J., Lanier L.L. Natural killer cells and cancer. Adv. Cancer Res. 2003; 90: 127-56.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2014 Eco-Vector


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: 

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies