caa a22 4500 605507252 CHVBK 20210128100631.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s00775-015-1242-x doi (NATIONALLICENCE)springer-10.1007/s00775-015-1242-x 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 [Elektronische Daten] [Miljana Momcilovic, Thomas Eichhorn, Jana Blazevski, Harry Schmidt, Goran Kaluđerović, Stanislava Stosic-Grujicic] 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. SBIC, 2015 Ruthenium(II) nationallicence T helper cell nationallicence Differentiation nationallicence Inflammation nationallicence Cytokine nationallicence Momcilovic Miljana Department of Immunology, Institute for Biological Research "Sinisa Stankovic”, University of Belgrade, Bulevar Despota Stefana 142, 11060, Belgrade, Serbia aut Eichhorn Thomas Institute of Chemistry, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Straße 2, 06120, Halle, Germany aut Blazevski Jana Department of Immunology, Institute for Biological Research "Sinisa Stankovic”, University of Belgrade, Bulevar Despota Stefana 142, 11060, Belgrade, Serbia aut Schmidt Harry Institute of Chemistry, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Straße 2, 06120, Halle, Germany aut Kaluđerović Goran Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120, Halle (Saale), Germany aut Stosic-Grujicic Stanislava Department of Immunology, Institute for Biological Research "Sinisa Stankovic”, University of Belgrade, Bulevar Despota Stefana 142, 11060, Belgrade, Serbia aut JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/3(2015-04-01), 575-583 0949-8257 20:3<575 2015 20 775 https://doi.org/10.1007/s00775-015-1242-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00775-015-1242-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Momcilovic Miljana Department of Immunology, Institute for Biological Research "Sinisa Stankovic”, University of Belgrade, Bulevar Despota Stefana 142, 11060, Belgrade, Serbia aut NATIONALLICENCE 700 1- Eichhorn Thomas Institute of Chemistry, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Straße 2, 06120, Halle, Germany aut NATIONALLICENCE 700 1- Blazevski Jana Department of Immunology, Institute for Biological Research "Sinisa Stankovic”, University of Belgrade, Bulevar Despota Stefana 142, 11060, Belgrade, Serbia aut NATIONALLICENCE 700 1- Schmidt Harry Institute of Chemistry, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Straße 2, 06120, Halle, Germany aut NATIONALLICENCE 700 1- Kaluđerović Goran Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120, Halle (Saale), Germany aut NATIONALLICENCE 700 1- Stosic-Grujicic Stanislava Department of Immunology, Institute for Biological Research "Sinisa Stankovic”, University of Belgrade, Bulevar Despota Stefana 142, 11060, Belgrade, Serbia aut NATIONALLICENCE 773 0- JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/3(2015-04-01), 575-583 0949-8257 20:3<575 2015 20 775