Influence of bacterial lectin on key regulatory links of functional activity of macrophages in mice with Ehrlich carcinoma

Authors

  • A.V. Chumak R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • N.I. Fedosova R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • V.M. Shcherbina R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • N.L. Cheremshenko R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • O.M. Karaman R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • V.F. Chekhun R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology

DOI:

https://doi.org/10.32471/exp-oncology.2312-8852.vol-43-no-3.16537

Keywords:

Ehrlich carcinoma, functional state, lectin from B. subtilis IMV B-7724, M1 and M2 polarization, peritoneal macrophages, transcription factors

Abstract

Summary. Background: Recent studies have shown the potential of using different approaches for immunotherapy in cancer treatment. Macrophages (Mph) are one of the promising targets for immunotherapy. Aim: To investigate changes in the functional activity of Mph in mice with Ehrlich carcinoma by nitric oxide (NO)/arginase (Arg), IRF4/IRF5 and STAT1/STAT6 ratios caused by administration of lectin from B. subtilis IMV-7724. Materials and Methods: From the 2nd day after Ehrlich carcinoma inoculation into female Balb/c mice, lectin from B. subtilis IMV B-7724 (0.02 mg/mouse) was administered for 10 days. The peritoneal Mph were isolated on days 14, 21, and 28 after tumor transplantation and their functional state (NO production, Arg activity and cytotoxic activity) was examined. The levels of mRNA expression of transcription factors STAT-1, STAT-6, IRF5, IRF4 were evaluated. Results: In lectin-treated animals with Ehrlich carcinoma, the functional state of Mph (NO/Arg ratio, index of cytotoxic activity) was maintained at the level of intact mice exceeding the values in untreated animals with Ehrlich carcinoma at late terms of tumor growth (21, 28 days). Analysis of mRNA expression levels of transcription factors in these animals showed a significant increase (p < 0.05) in the ratio of STAT1/STAT6 on the day 21 and IRF5/IRF4 on day 28 of tumor growth compared to that in untreated mice. Conclusions: Administration of lectin from B. subtilis IMV B-7724 to mice with Ehrlich carcinoma led to the prevalence of Mph exhibiting the functional properties of M1 type at late-term tumor growth. The transcription factors of the STAT and IRF signaling pathways are involved in the process of Mph polarization induced by lectin from B. subtilis IMV B-7724.

References

Kovaleva OV, Mikhailenko DS, Alekseev BYa, Grachev AN. The role of tumor-associated macrophages in the pathogenesis of renal cell carcinoma 2017; 1: 20–6 (in Russian). https://doi.org/10.17 650 / 1726-9776-2017-13-1-20-26.

Lyamina S.V. Polarization of macrophages in the modern concept of the formation of the immune response. Fundamental’nyye Issledovaniya 2014; 10: 930–5 (in Russian). ISSN 1812-7339.

Jordan M,Waxman DJ. CpG-1826 immunotherapy potentiates chemotherapeutic and anti-tumor immune responses to metronomic cyclophosphamide in a preclinical glioma model. Cancer Lett 2016; 373: 88–96. https://doi.org/10.1016/j.canlet.2015.11.029.

Le Noci V, Tortoreto M, Gulino A, et al. Poly(I:C) and CpG-ODN combined aerosolization to treat lung metastases and counter the immunosuppressive microenvironment. Oncoimmunology 2015; 4: e1040214. https://doi.org/10.1080/2162402X.2015.1040214.

Daei Farshchi Adli A, Jahanban-Esfahlan R, Seidi K, et al. An overview on Vadimezan (DMXAA): The vascular disrupting agent. Chem Biol Drug Des 2018; 91: 996–1006. https://doi.org/10.1111/cbdd.13166.

Kaneda MM, Messer KS, Ralainirina N, et al. PI3Kgamma is a molecular switch that controls immune suppression. Nature 2016; 539: 437–42. https://doi.org/10.1038/nature19834.

Pan Y, Yu Y, Wang X, et al. Tumor-associated macrophages in tumor immunity. Front Immunol 2020; 11: 583084. https://doi.org/10.3389/fimmu.2020.583084.

Fraternale A BS, Magnani M. Polarization and repolarization of macrophages. Clin Cell Immunol 2015; 6: 1–6. https://doi.org/10.4172/2155-9899.1000319.

Chai ZT, Zhu XD, Ao JY, et al. microRNA-26a suppresses recruitment of macrophages by down-regulating macrophage colony-stimulating factor expression through the PI3K/Akt pathway in hepatocellular carcinoma. J Hematol Oncol 2015; 8: 56. https://doi.org/10.1186/s13045-015-0150-4.

Garaci E, Pica F, Sinibaldi-Vallebona P, et al. Thymosin alpha(1) in combination with cytokines and chemotherapy for the treatment of cancer. Int Immunopharmacol 2003; 3: 1145–50. https://doi.org/10.1016/S1567-5769(03)00053-5.

Liu M, Luo F, Ding C, et al. Correction: dectin-1 activation by a natural product beta-glucan converts immunosuppressive macrophages into an m1-like phenotype. J Immunol 2016; 196: 3968. https://doi.org/10.4049/jimmunol.1600345.

Chekhun VF, Didenko GV, Cheremshenko NL, et al. [Strain of bacteria Bacillus subtilis IMB B-7724 — producer of cytotoxic substances with antitumor activity] (Patent UA 131824). Publ. 25.01.2019 (in Ukrainian).

Podgorsky VS. The method for the obtaining bacterial lectin, specific to sialic acids (Patent UA 1791 ). Publ. 23.01.1991. (in Ukrainian).

Kozhemyakin UM, Filonenko MA, Saifetdinova GA. Scientific and Practical Recommendations for Keeping Laboratory Animals and Working with Them. K: Avicenna 2002; 156 p (in Ukrainian).

van de Loosdrecht AA Beelen RH, Ossenkoppele GJ. A tetrazolium-based colorimetric MTT assay to quantitate human monocyte mediated cytotoxicity against leukemic cells from cell lines and patients with acute myeloid leukemia. J Immunol Met 1994; 174: 311–20. https://doi.org/10.1016/0022-1759(94)90034-5.

Reiner NE. Methods in molecular biology. Macrophages and dendritic cells. Methods and protocols. Preface. Methods Mol Biol 2009; 531. https://doi.org/10.1007/978-1-59745-396-7.

Dovgiy RS, Shitikov, DV, Pishel, IN, et al. Functional state and metabolic polarization of splenic macrophages of old immunized mice. Problemy Stareniya Dolgoletiya 2015; 24: 111–9. ISSN 08691703 (in Ukrainian).

Horhold F, Eisel D, Oswald M, et al. Reprogramming of macrophages employing gene regulatory and metabolic network models. PLoS Comput Biol 2020; 16: e1007657. https://doi.org/10.1371/journal.pcbi.1007657.

Zhou J, Li Z, Wu T, et al. LncGBP9/miR-34a axis drives macrophages toward a phenotype conducive for spinal cord injury repair via STAT1/STAT6 and SOCS3. J Neuroinflammation 2020; 17: 134. https://doi.org/10.1186/s12974-020-01805-5.

van Dalen FJ, van Stevendaal M, Fennemann FL, et al. Molecular repolarisation of tumour-associated macrophages. Molecules 2018; 24: 9. https://doi.org/10.3390/molecules24010009.

Li D, De S, Li D, et al. Specific detection of interferon regulatory factor 5 (IRF5): A case of antibody inequality. Sci Rep 2016; 6: 31002. https://doi.org/10.1038/srep31002.

Weiss M, Blazek K, Byrne AJ, et al. IRF5 is a specific marker of inflammatory macrophages in vivo. Mediators Inflamm 2013; 2013: 245804. https://doi.org/10.1155/2013/245804.

Almuttaqi H, Udalova IA. Advances and challenges in targeting IRF5, a key regulator of inflammation. FEBS J 2019; 286: 1624–37. https://doi.org/10.1111/febs.14654.

Arora S, Dev K, Agarwal B, et al. Macrophages: Their role, activation and polarization in pulmonary diseases. Immunobiology 2018; 223: 383–96. https://doi.org/10.1016/j.imbio.2017.11.001.

Liu YC, Zou XB, Chai YF, et al. Macrophage polarization in inflammatory diseases. Int J Biol Sci 2014; 10: 520–9. https://doi.org/10.7150/ijbs.8879.

Tugal D, Liao X, Jain MK. Transcriptional control of macrophage polarization. Arterioscler Thromb Vasc Biol 2013; 33: 1135–44. https://doi.org/10.1161/ATVBAHA.113.301453.

Baghban R, Roshangar L, Jahanban-Esfahlan R, et al. Tumor microenvironment complexity and therapeutic implications at a glance. Cell Commun Signal 2020; 18: 59. https://doi.org/10.1186/s12964-020-0530-4.

Hong IS. Stimulatory versus suppressive effects of GM-CSF on tumor progression in multiple cancer types. Exp Mol Med 2016; 48: e242. https://doi.org/10.1038/emm.2016.64.

Jeannin P, Paolini L, Adam C, et al. The roles of CSFs on the functional polarization of tumor-associated macrophages. FEBS J 2018; 285: 680–99. https://doi.org/10.1111/febs.14343.

Abdolvahab MH, Darvishi B, Zarei M, et al. Interferons: role in cancer therapy. Immunotherapy 2020; 12: 833–55. https://doi.org/10.2217/imt-2019-0217.

Budhwani M, Mazzieri R, Dolcetti R. Plasticity of type I interferon-mediated responses in cancer therapy: from anti-tumor immunity to resistance. Front Oncol 2018; 8: 322. https://doi.org/10.3389/fonc.2018.00322.

Ali S, Mann-Nuttel R, Schulze A, et al. Sources of type I interferons in infectious immunity: plasmacytoid dendritic cells not always in the driver’s seat. Front Immunol 2019; 10: 778. https://doi.org/10.3389/fimmu.2019.00778.

Symchych TV, Fedosova NI, Chumak AV, et al. Functions of tumor-associated macrophages and macrophages residing in remote anatomical niches in Ehrlich carcinoma bearing mice. Exp Oncol 2020; 42: 197–203. https://doi.org/10.32471/exp-oncology.2312-8852.vol-42-no-3.14928.

Podgorskii VS, Kovalenko EA, Karpova IS, et al. [Extracellular lectins from saprophytic strains of bacteria of the genus Bacillus (review)]. Prikl Biokhim Mikrobiol 2014; 50: 256–63 (in Russian). https://doi.org/10.1134/S0003683814030120.

Piaszyk-Borychowska A, Szeles L, Csermely A, et al. Signal integration of IFN-I and IFN-II with TLR4 involves sequential recruitment of STAT1-complexes and NFkappaB to enhance pro-inflammatory transcription. Front Immunol 2019; 10: 1253. https://doi.org/10.3389/fimmu.2019.01253.

Chumak A, Shcherbina V, Fedosova N, Chekhun V. Polarization of macrophages of mice under the influence of lectin from Bacillus subtilis IMV B-7724. EUREKA: Life Sci 2021; 43: 15–20. https://doi.org/10.21303/2504-5695.2021.001878.

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Published

26.05.2023

How to Cite

Chumak, A., Fedosova, N., Shcherbina, V., Cheremshenko, N., Karaman, O., & Chekhun, V. (2023). Influence of bacterial lectin on key regulatory links of functional activity of macrophages in mice with Ehrlich carcinoma. Experimental Oncology, 43(3), 197–203. https://doi.org/10.32471/exp-oncology.2312-8852.vol-43-no-3.16537

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