In vitro immunomodulatory activity of ruthenium complexes
| Autor: | J. C. Jenson, Paul G. Gregory, K. A. Gordon, B. Rivnay, M Jesson, J. R. Newcomb, S. M. Turci, J. Krieger, B. Jones, C. M. Bastos, Timothy D. Ocain, K. A. Sterne |
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| Rok vydání: | 2003 |
| Předmět: |
Pyridines
T-Lymphocytes T cell Immunology Fluorescent Antibody Technique macromolecular substances In Vitro Techniques Biology Resting Phase Cell Cycle Cell Line S Phase Dogs Immune system Tetanus Toxoid medicine Animals Humans Cytotoxic T cell IL-2 receptor Antigen-presenting cell Cytotoxicity Sirolimus Pharmacology B-Lymphocytes Immunity Cellular Superantigens T-cell receptor G1 Phase Imidazoles Receptors Interleukin-2 DNA Ruthenium Red Cell biology medicine.anatomical_structure Cell culture Cyclosporine Interleukin-2 Ruthenium Compounds Lymphocyte Culture Test Mixed Cell Division Immunosuppressive Agents |
| Zdroj: | Inflammation Research. 52:263-271 |
| ISSN: | 1023-3830 |
| Popis: | Objective and Design: We have explored the in vitro immunomodulatory effects of pure ruthenium red and a series of pyridine and imidazole substituted ruthenium complexes (RCs). Material: Human peripheral blood lymphocytes and purified T cells were used in these studies along with various cell lines. Methods: Cells were treated with dilutions of RCs and assessed in various assays of immune function, cytotoxicity and cell cycle progression. Results: RCs efficiently blocked T cell receptor (TCR)-mediated stimulation (IC50's in the low nM range) of human peripheral blood lymphocytes (hPBL) by various agents, including tetanus toxoid, alloantigens, superantigens, and receptor-specific antibodies. RCs are not cytotoxic to T cells. Antiproliferative activity was also observed for B cells. Some non-lymphoid cell lines or primary cultures showed sensitivity to the RCs, but only at higher concentrations. The inhibitory effect on human T cells was assessed and demonstrated at the level of proliferation (DNA synthesis), IL-2 secretion, and IL-2 receptor (CD25) upregulation. RCs also inhibited IL-2-mediated proliferation of antigen-induced T-cell blasts and the IL-2-dependent T cell line Kit-225. Cell cycle analysis indicates that RCs inhibit the progression of activated T cells from G0/G1 to S phase. Conclusions: Since the mechanism of T cell inhibition by RCs appears to be different than that of rapamycin (RAP) or cyclosporin A (CsA), they may provide a new tool to investigate intracellular signaling in T cells, and may present novel opportunities for immunosuppression |
| Databáze: | OpenAIRE |
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