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Ruthenium pyridyl thiocyanate complex increased the production of pro-inflammatory TNFα and IL1β cytokines by the LPS stimulated mammalian macrophages in vitro

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Abstract

Every cell in our body depends on the electron transport processes in order to generate energy and function properly. Being able to regulate the metabolic activity of a cell would enable us altering its function and eventually lead us to a desired biological outcome at the cellular level and more desirably at a systemic level. Immunomodulatory or immunostimulatory molecules have been focus of the recent studies in order to regulate or boost the activities of the immune system cells and suppress or eliminate the disease conditions such as cancer, autoimmune reactions, inflammatory disorders as well as infections. In our study we used a ruthenium pyridyl thiocyanate complex, K330, to examine its effect on the activity of the innate immune system cells, macrophages in vitro. K330 was our candidate due to its application in the solar cells. Especially, due to its ability to get involved in electron transfer systems we hypothesized that it could change the activity of the immune system cells at cellular level, possibly by interfering the electron transfer reactions of the cells. Our results support our hypothesis since K330 lead to a significant increase in TNFα and IL1β cytokine production levels by LPS stimulated macrophages compared to only LPS treated control groups. Based on our in vitro results, K330 can also be utilized as an adjuvant candidate in vaccinations where the antigen itself is not sufficient to generate a proper immune response.

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Abbreviations

TNF-α:

Tumor nacrosis factor-α

IL-6:

Interleukin 6

IL1β:

Interleukin 1β

RAW 264.7:

Mouse macrophage cell line

ELISA:

Enzyme linked immunosorbent assay

LPS:

Lipopolysachharide

References

  1. Ocakoglu K, Sogut S, Sarica H, Guloglu P, Erten-Ela S, Emen FM (2013) Influences of the electron donor groups on the properties of thiophene-pyrrole-thiophene and tert-butyl based new ruthenium II bipyridyl sensitizers for DSSCs and DFT studies. Synth Metals 174:24–32. https://doi.org/10.1016/j.synthmet.2013.04.016

    Article  CAS  Google Scholar 

  2. Ocakoglu K, Zafer C, Cetinkaya B, Icli S (2007) Synthesis, characterization, electrochemical and spectroscopic studies of two new heteroleptic Ru(II) polypyridyl complexes. Dyes Pigm 75:385–394. https://doi.org/10.1016/j.dyepig.2006.06.016

    Article  CAS  Google Scholar 

  3. Ocakoglu K, Harputlu E, Guloglu P, Erten-Ela S (2012) The photovoltaic performance of new ruthenium complexes in DSSCs based on nanorod ZnO electrode. Synth Metals. https://doi.org/10.1016/j.synthmet.2012.10.006

    Article  Google Scholar 

  4. Buck MD, Sowell RT, Kaech SM, Pearce EL (2017) Metabolic instruction of immunity. Cell 169:570–586, https://doi.org/10.1016/j.cell.2017.04.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Arango Duque G, Descoteaux A (2014) Macrophage cytokines: involvement in immunity and infectious diseases. Front Immunol 5:491. https://doi.org/10.3389/fimmu.2014.00491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Murray RZ, Stow JL (2014) Cytokine secretion in macrophages: SNAREs, Rabs, and membrane trafficking. Front Immunol 5:538. https://doi.org/10.3389/fimmu.2014.00538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kawagishi C, Kurosaka K, Watanabe N, Kobayashi Y (2001) Cytokine production by macrophages in association with phagocytosis of etoposide-treated P388 cells in vitro and in vivo. Biochim Biophys Acta 1541(3):221–230. https://doi.org/10.1016/S0167-4889(01)00158-6

    Article  CAS  PubMed  Google Scholar 

  8. Cavaillon JM, (1994) Cytokines and macrophages. Biomed Pharmacother 48(10):445–453. https://doi.org/10.1016/0753-3322(94)90005-1

    Article  CAS  PubMed  Google Scholar 

  9. Scull CM, Hays WD, Fischer TH (2010) Macrophage proinflammatory cytokine secretion is enhanced following interaction with autologous platelets. J Inflam 7:53. https://doi.org/10.1186/1476-9255-7-53

    Article  CAS  Google Scholar 

  10. Berghaus LJ, Moore JN, Hurley DJ, Vandenplas ML, Fortes BP, Wolfert MA, Boons GJ (2010) Innate immune responses of primary murine macrophage-lineage cells and RAW 264.7 cells to ligands of Toll-like receptors 2, 3, and 4. Comp Immunol Microbiol Infect Dis 33(5):443–454

    Article  Google Scholar 

  11. Schmitz F, Mages J, Heit A, Lang R, Wagner H (2004) Transcriptional activation induced in macrophages by Toll-like receptor (TLR) ligands: from expression profiling to a model of TLR signaling. Eur J Immunol 34(10):2863–2873

    Article  CAS  Google Scholar 

  12. Soromou LW, Zhang Z, Li R, Chen N, Guo W, Huo M, Guan S, Lu J, Deng X (2012) Regulation of inflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 murine macrophage by 7-O-methyl-naringenin. Molecules 17(3):3574–3585

    Article  CAS  Google Scholar 

  13. Gasparini C, Foxwell BM, Feldmann M (2013) RelB/p50 regulates TNF production in LPS-stimulated dendritic cells and macrophages. Cytokine 61(3):736–740

    Article  CAS  Google Scholar 

  14. Parameswaran N, Patial S (2010) Tumor necrosis factor-α signaling in macrophages. Crit Rev Eukaryot Gene Expr 20(2):87–103

    Article  CAS  Google Scholar 

  15. Lopez-Castejon G, Brough D (2011) Understanding the mechanism of IL-1β secretion. Cytokine Growth Factor Rev 22(4):189–195. https://doi.org/10.1016/j.cytogfr.2011.10.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Manderson AP, Kay JG, Hammond LA, Brown DL, Stow JL (2007) Subcompartments of the macrophage recycling endosome direct the differential secretion of IL-6 and TNFα. J Cell Biol 178(1):57. https://doi.org/10.1083/jcb.200612131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zaccone P et al (1999 Jun) The involvement of IL-12 in murine experimentally induced autoimmune thyroid disease. Eur J Immunol 29(6):1933–1942

    Article  CAS  Google Scholar 

  18. Zaccone P et al (2005) IL-18 binding protein fusion construct delays the development of diabetes in adoptive transfer and cyclophosphamide-induced diabetes in NOD mouse. Clin Immunol 115(1):74–79

    Article  CAS  Google Scholar 

  19. Nicoletti F et al (1997) Prevention of spontaneous autoimmune diabetes in diabetes-prone BB rats by prophylactic treatment with antirat interferon-gamma antibody. Endocrinology 138(1):281–288

    Article  CAS  Google Scholar 

  20. Fagone P et al (2018) Contribution of the macrophage migration inhibitory factor superfamily of cytokines in the pathogenesis of preclinical and human multiple sclerosis: in silico and in vivo evidences. J Neuroimmunol 322:46–56. https://doi.org/10.1016/j.jneuroim.2018.06.009

    Article  CAS  PubMed  Google Scholar 

  21. Su LC et al (2018) Emerging role of IL-35 in inflammatory autoimmune diseases. Autoimmun Rev 17(7):665–673. https://doi.org/10.1016/j.autrev.2018.01.017

    Article  CAS  PubMed  Google Scholar 

  22. Lee PW et al (2017 Mar) TGF-β regulation of encephalitogenic and regulatory T cells in multiple sclerosis. Eur J Immunol 47(3):446–453. https://doi.org/10.1002/eji.201646716

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Nicoletti F et al (1998 Jul) Blood levels of transforming growth factor-beta 1 (TGF-beta1) are elevated in both relapsing remitting and chronic progressive multiple sclerosis (MS) patients and are further augmented by treatment with interferon-beta 1b (IFN-beta1b). Clin Exp Immunol 113(1):96–99

    Article  CAS  Google Scholar 

  24. Broide DH (2009) Immunomodulation of allergic disease. Annu Rev Med 60:279–291

    Article  CAS  Google Scholar 

  25. Iwalewa EO, McGaw LJ, Naidoo V, Eloff JN (2007) Inflammation: the foundation of diseases and disorders. A review of phytomedicines of South African origin used to treat pain and inflammatory condition. Afr J Biotechnol 6(25):2868–2885

    Article  CAS  Google Scholar 

  26. Hancock REW, Nijnik A, Philpott DJ (2012) Modulating immunity as a therapy for bacterial infections. Nat Rev Microbiol 10:243–254

    Article  CAS  Google Scholar 

  27. Kaufmann, T, Simon H (2015) U. Targeting disease by immunomodulation. Cell Death Differ 22:185–186

    Article  CAS  Google Scholar 

  28. Julier Z, Park AJ, Briquez PS, Martino MM (2017) Promoting tissue regeneration by modulating the immune system Acta Biomaterialia 53:13–28

    Article  CAS  Google Scholar 

  29. Khalil DN, Smith EL, Brentjens RJ, Wolchok JD (2016) The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol 13(5):273–290. https://doi.org/10.1038/nrclinonc.2016.25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tan TT, Coussens LM (2007) Humoral immunity, inflammation and cancer. Curr Opin Immunol 19(2):209–216. https://doi.org/10.1016/j.coi.2007.01.001

    Article  CAS  PubMed  Google Scholar 

  31. Daniel CS, Ira M (2013) Oncology meets immunity. Immunity 39(1):1–10. https://doi.org/10.1016/j.immuni.2013.07.012

    Article  CAS  Google Scholar 

  32. Guevara-Patiño JA, Turk MJ, Wolchok JD, Houghton AN (2003) Immunity to cancer through immune recognition of altered self: studies with melanoma. Adv Cancer Res. 90:157–177. https://doi.org/10.1016/S0065-230X(03)90005-4

    Article  PubMed  Google Scholar 

  33. Valdés-Ramos R, Benítez-Arciniega A (2007) Nutrition and immunity in cancer. Br J Nutr 98(S1):S127–S132. https://doi.org/10.1017/S0007114507833009

    Article  CAS  PubMed  Google Scholar 

  34. Grivennikov SI, Greten FR, Karin M, (2010) Immunity inflammation, and cancer. Cell 140(6):883–899. https://doi.org/10.1016/j.cell.2010.01.025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Rakoff-Nahoum S (2006) Why cancer and inflammation? Yale J Biol Med 79(3–4):123–130

    CAS  PubMed  Google Scholar 

  36. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867. https://doi.org/10.1038/nature01322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Nicoletti F et al (1997 Jun) Prevention of endotoxin-induced lethality in neonatal mice by interleukin-13. Eur J Immunol 27(6):1580–1583

    Article  CAS  Google Scholar 

  38. Gérard C et al (1993) Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia. J Exp Med 177(2):547–550

    Article  Google Scholar 

  39. Raphael I, Nalawade S, Eagar TN, Forsthuber TG (2015) T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine 74(1):5–17. https://doi.org/10.1016/j.cyto.2014.09.011

    Article  CAS  PubMed  Google Scholar 

  40. Dujmovic I et al (2009) The analysis of IL-1 beta and its naturally occurring inhibitors in multiple sclerosis: the elevation of IL-1 receptor antagonist and IL-1 receptor type II after steroid therapy. J Neuroimmunol 207(1–2):101–106. https://doi.org/10.1016/j.jneuroim.2008.11.004

    Article  CAS  PubMed  Google Scholar 

  41. Dayer JM (2018) From supernatants to cytokines: a personal view on the early history of IL-1, IL-1Ra, TNF and its inhibitor in rheumatology. Arthritis Res Ther 20(1):101. https://doi.org/10.1186/s13075-018-1607-y

    Article  PubMed  PubMed Central  Google Scholar 

  42. Karin N et al (2018) Autoantibodies to chemokines and cytokines participate in the regulation of cancer and autoimmunity. Front Immunol. 9:623. https://doi.org/10.3389/fimmu.2018.00623. (eCollection 2018)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Barcellini W (1996 Apr) In vitro type-1 and type-2 cytokine production in systemic lupus erythematosus: lack of relationship with clinical disease activity. Lupus 5(2):139–145

    Article  CAS  Google Scholar 

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Acknowledgements

I greatly appreciate the material supports of Prof. Dr. Kasım Ocakoglu from Tarsus University and Prof. Dr. Juan Anguita from CICBiogune.

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Correspondence to Furkan Ayaz.

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Ayaz, F. Ruthenium pyridyl thiocyanate complex increased the production of pro-inflammatory TNFα and IL1β cytokines by the LPS stimulated mammalian macrophages in vitro. Mol Biol Rep 45, 2307–2312 (2018). https://doi.org/10.1007/s11033-018-4392-4

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  • DOI: https://doi.org/10.1007/s11033-018-4392-4

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