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In vitro effects of binuclear ( η- 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.
- Source :
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Journal of Biological Inorganic Chemistry (JBIC) . Apr2015, Vol. 20 Issue 3, p575-583. 9p. - Publication Year :
- 2015
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Abstract
- 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 [{RuCl(η- p-cym)}μ-(NN)] (NN = bis(nicotinate)- and bis(iso-nicotinate)-polyethylene glycol esters; (3-py)COO(CHCHO)CO(3-py) and (4-py)COO(CHCHO)CO(4-py); n = 1-4), as well as [RuCl(η- p-cym)(nic)] ( R1, nic = nicotinate) and [RuCl(η- p-cym)(inic)] ( R2, inic = isonicotinate) as an immunomodulatory agents capable to direct Th cell differentiation. From all investigated complexes, [{RuCl(η- p-cym)}μ-{(3-py)COO(CHCHO)CO(3-py)}] ( 4) was selected for further study because it did not affect splenocyte viability (in concentration up to 50 μM), 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 CD4CD25FoxP3 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09498257
- Volume :
- 20
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Inorganic Chemistry (JBIC)
- Publication Type :
- Academic Journal
- Accession number :
- 101832135
- Full Text :
- https://doi.org/10.1007/s00775-015-1242-x