Molecular Biology Reports

, Volume 45, Issue 6, pp 2307–2312 | Cite as

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

  • Furkan AyazEmail author
Original Article


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.


TNF-α IL-6 IL-1β Inflammation Macrophage Immunomodulation Adjuvants Innate immunity 



Tumor nacrosis factor-α


Interleukin 6


Interleukin 1β

RAW 264.7

Mouse macrophage cell line


Enzyme linked immunosorbent assay





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

Compliance with ethical standards

Conflict of interest

The author declare no competing financial or non-financial conflict of interest.


  1. 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. CrossRefGoogle Scholar
  2. 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. CrossRefGoogle Scholar
  3. 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. CrossRefGoogle Scholar
  4. 4.
    Buck MD, Sowell RT, Kaech SM, Pearce EL (2017) Metabolic instruction of immunity. Cell 169:570–586, CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Arango Duque G, Descoteaux A (2014) Macrophage cytokines: involvement in immunity and infectious diseases. Front Immunol 5:491. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Murray RZ, Stow JL (2014) Cytokine secretion in macrophages: SNAREs, Rabs, and membrane trafficking. Front Immunol 5:538. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 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. CrossRefPubMedGoogle Scholar
  8. 8.
    Cavaillon JM, (1994) Cytokines and macrophages. Biomed Pharmacother 48(10):445–453. CrossRefPubMedGoogle Scholar
  9. 9.
    Scull CM, Hays WD, Fischer TH (2010) Macrophage proinflammatory cytokine secretion is enhanced following interaction with autologous platelets. J Inflam 7:53. CrossRefGoogle Scholar
  10. 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):443–454CrossRefGoogle Scholar
  11. 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):2863–2873CrossRefGoogle Scholar
  12. 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):3574–3585CrossRefGoogle Scholar
  13. 13.
    Gasparini C, Foxwell BM, Feldmann M (2013) RelB/p50 regulates TNF production in LPS-stimulated dendritic cells and macrophages. Cytokine 61(3):736–740CrossRefGoogle Scholar
  14. 14.
    Parameswaran N, Patial S (2010) Tumor necrosis factor-α signaling in macrophages. Crit Rev Eukaryot Gene Expr 20(2):87–103CrossRefGoogle Scholar
  15. 15.
    Lopez-Castejon G, Brough D (2011) Understanding the mechanism of IL-1β secretion. Cytokine Growth Factor Rev 22(4):189–195. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Zaccone P et al (1999 Jun) The involvement of IL-12 in murine experimentally induced autoimmune thyroid disease. Eur J Immunol 29(6):1933–1942CrossRefGoogle Scholar
  18. 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):74–79CrossRefGoogle Scholar
  19. 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):281–288CrossRefGoogle Scholar
  20. 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. CrossRefPubMedGoogle Scholar
  21. 21.
    Su LC et al (2018) Emerging role of IL-35 in inflammatory autoimmune diseases. Autoimmun Rev 17(7):665–673. CrossRefPubMedGoogle Scholar
  22. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 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):96–99CrossRefGoogle Scholar
  24. 24.
    Broide DH (2009) Immunomodulation of allergic disease. Annu Rev Med 60:279–291CrossRefGoogle Scholar
  25. 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):2868–2885CrossRefGoogle Scholar
  26. 26.
    Hancock REW, Nijnik A, Philpott DJ (2012) Modulating immunity as a therapy for bacterial infections. Nat Rev Microbiol 10:243–254CrossRefGoogle Scholar
  27. 27.
    Kaufmann, T, Simon H (2015) U. Targeting disease by immunomodulation. Cell Death Differ 22:185–186CrossRefGoogle Scholar
  28. 28.
    Julier Z, Park AJ, Briquez PS, Martino MM (2017) Promoting tissue regeneration by modulating the immune system Acta Biomaterialia 53:13–28CrossRefGoogle Scholar
  29. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Tan TT, Coussens LM (2007) Humoral immunity, inflammation and cancer. Curr Opin Immunol 19(2):209–216. CrossRefPubMedGoogle Scholar
  31. 31.
    Daniel CS, Ira M (2013) Oncology meets immunity. Immunity 39(1):1–10. CrossRefGoogle Scholar
  32. 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. CrossRefPubMedGoogle Scholar
  33. 33.
    Valdés-Ramos R, Benítez-Arciniega A (2007) Nutrition and immunity in cancer. Br J Nutr 98(S1):S127–S132. CrossRefPubMedGoogle Scholar
  34. 34.
    Grivennikov SI, Greten FR, Karin M, (2010) Immunity inflammation, and cancer. Cell 140(6):883–899. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Rakoff-Nahoum S (2006) Why cancer and inflammation? Yale J Biol Med 79(3–4):123–130PubMedGoogle Scholar
  36. 36.
    Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867. CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Nicoletti F et al (1997 Jun) Prevention of endotoxin-induced lethality in neonatal mice by interleukin-13. Eur J Immunol 27(6):1580–1583CrossRefGoogle Scholar
  38. 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):547–550CrossRefGoogle Scholar
  39. 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. CrossRefPubMedGoogle Scholar
  40. 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. CrossRefPubMedGoogle Scholar
  41. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Karin N et al (2018) Autoantibodies to chemokines and cytokines participate in the regulation of cancer and autoimmunity. Front Immunol. 9:623. (eCollection 2018)CrossRefPubMedPubMedCentralGoogle Scholar
  43. 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):139–145CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Department of Biotechnology, Faculty of Arts and ScienceMersin UniversityMersinTurkey

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