In vitro effects of binuclear ( η 6- p -cymene)ruthenium(II) complex containing bridging bis(nicotinate)-polyethylene glycol ester ligand on differentiation pathways of murine Th lymphocytes activated by T cell mitogen
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| 024 | 7 | 0 | |a 10.1007/s00775-015-1242-x |2 doi |
| 035 | |a (NATIONALLICENCE)springer-10.1007/s00775-015-1242-x | ||
| 245 | 0 | 0 | |a In vitro effects of binuclear ( η 6- p -cymene)ruthenium(II) complex containing bridging bis(nicotinate)-polyethylene glycol ester ligand on differentiation pathways of murine Th lymphocytes activated by T cell mitogen |h [Elektronische Daten] |c [Miljana Momcilovic, Thomas Eichhorn, Jana Blazevski, Harry Schmidt, Goran Kaluđerović, Stanislava Stosic-Grujicic] |
| 520 | 3 | |a T cell differentiation into distinct T helper (Th) subpopulations is crucial in governing acquired immune responses as well as some inflammatory and autoimmune disorders. This study investigated potential of the novel neutral binuclear ruthenium(II) complexes 1-8 with general formula [{RuCl2(η6-p-cym)}2μ-(N∩N)] (N∩N=bis(nicotinate)- and bis(iso-nicotinate)-polyethylene glycol esters; (3-py)COO(CH2CH2O) n CO(3-py) and (4-py)COO(CH2CH2O) n CO(4-py); n=1-4), as well as [RuCl2(η6-p-cym)(nic)] (R1, nic=nicotinate) and [RuCl2(η6-p-cym)(inic)] (R2, inic=isonicotinate) as an immunomodulatory agents capable to direct Th cell differentiation. From all investigated complexes, [{RuCl2(η6-p-cym)}2μ-{(3-py)COO(CH2CH2O)4CO(3-py)}] (4) was selected for further study because it did not affect splenocyte viability (in concentration up to 50μM), but significantly reduced secretion of representative Th1 cytokine, IFN-γ induced by T cell mitogen. Besides IFN-γ, 4 inhibited dose dependently expression and production of representative Th17 cytokine, IL-17, in these cells. Otherwise, the production of anti-inflammatory cytokines IL-4 and IL-10 was upregulated. Also, 4 significantly increased CD4+CD25+FoxP3+ Treg cell frequency in the activated splenocytes. Moreover, ConA-induced expression of Th1 transcription factors, T-bet and STAT1, as well as of Th17-related protein STAT3 was attenuated upon exposure to 4, while the expression of Th2-related transcription factor GATA3 remained stable. In conclusion, ruthenium(II) complex 4 modulates immune system cell functions in vitro by inhibiting T cell differentiation towards pathogenic Th1/Th17 phenotype and inducing a regulatory phenotype characterized by IL-10 and IL-4 production, which may provide novel therapeutic opportunities for immune-inflammatory and/or autoimmune disorders. | |
| 540 | |a SBIC, 2015 | ||
| 690 | 7 | |a Ruthenium(II) |2 nationallicence | |
| 690 | 7 | |a T helper cell |2 nationallicence | |
| 690 | 7 | |a Differentiation |2 nationallicence | |
| 690 | 7 | |a Inflammation |2 nationallicence | |
| 690 | 7 | |a Cytokine |2 nationallicence | |
| 700 | 1 | |a Momcilovic |D Miljana |u Department of Immunology, Institute for Biological Research "Sinisa Stankovic”, University of Belgrade, Bulevar Despota Stefana 142, 11060, Belgrade, Serbia |4 aut | |
| 700 | 1 | |a Eichhorn |D Thomas |u Institute of Chemistry, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Straße 2, 06120, Halle, Germany |4 aut | |
| 700 | 1 | |a Blazevski |D Jana |u Department of Immunology, Institute for Biological Research "Sinisa Stankovic”, University of Belgrade, Bulevar Despota Stefana 142, 11060, Belgrade, Serbia |4 aut | |
| 700 | 1 | |a Schmidt |D Harry |u Institute of Chemistry, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Straße 2, 06120, Halle, Germany |4 aut | |
| 700 | 1 | |a Kaluđerović |D Goran |u Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120, Halle (Saale), Germany |4 aut | |
| 700 | 1 | |a Stosic-Grujicic |D Stanislava |u Department of Immunology, Institute for Biological Research "Sinisa Stankovic”, University of Belgrade, Bulevar Despota Stefana 142, 11060, Belgrade, Serbia |4 aut | |
| 773 | 0 | |t JBIC Journal of Biological Inorganic Chemistry |d Springer Berlin Heidelberg |g 20/3(2015-04-01), 575-583 |x 0949-8257 |q 20:3<575 |1 2015 |2 20 |o 775 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00775-015-1242-x |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s00775-015-1242-x |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Momcilovic |D Miljana |u Department of Immunology, Institute for Biological Research "Sinisa Stankovic”, University of Belgrade, Bulevar Despota Stefana 142, 11060, Belgrade, Serbia |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Eichhorn |D Thomas |u Institute of Chemistry, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Straße 2, 06120, Halle, Germany |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Blazevski |D Jana |u Department of Immunology, Institute for Biological Research "Sinisa Stankovic”, University of Belgrade, Bulevar Despota Stefana 142, 11060, Belgrade, Serbia |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Schmidt |D Harry |u Institute of Chemistry, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Straße 2, 06120, Halle, Germany |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Kaluđerović |D Goran |u Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120, Halle (Saale), Germany |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Stosic-Grujicic |D Stanislava |u Department of Immunology, Institute for Biological Research "Sinisa Stankovic”, University of Belgrade, Bulevar Despota Stefana 142, 11060, Belgrade, Serbia |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t JBIC Journal of Biological Inorganic Chemistry |d Springer Berlin Heidelberg |g 20/3(2015-04-01), 575-583 |x 0949-8257 |q 20:3<575 |1 2015 |2 20 |o 775 | ||