Combination of immunosuppressive drugs leaves specific "fingerprint" on gene expression in vitro

Combination of immunosuppressive drugs leaves specific "fingerprint" on gene expression in vitro

Following organ transplantation many patients suffer from drug-related side effects, or receive more immunosuppression than necessary to prevent rejection. Hence, parameters are needed to tailor the immunosuppressive therapy to the individual needs of an organ recipient. The aim of this study was to...

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Bibliographic Details
Published in:Immunopharmacology and immunotoxicology Vol. 31; no. 2; pp. 283 - 292
Main Authors: Rumberger, Brigitta, Kreutz, Clemens, Nickel, Christian, Klein, Marinella, Lagoutte, Severine, Teschner, Sven, Timmer, Jens, Gerke, Peter, Walz, Gerd, Donauer, Johannes
Format: Journal Article
Language:English
Published: England Informa UK Ltd 01-06-2009
Taylor & Francis
Subjects:
Adult
Cells, Cultured
Cyclosporine - pharmacology
Cyclosporins
Data processing
DNA microarrays
Drug Interactions
Everolimus
Gene expression
Gene Expression - drug effects
Gene Expression Profiling
Graft rejection
Humans
Immune response
Immunosuppression
Immunosuppressive agents
Immunosuppressive Agents - pharmacology
Leaves
Lymphocyte Activation - drug effects
Lymphocytes
Lymphocytes - drug effects
Lymphocytes - immunology
Mycophenolic acid
Mycophenolic Acid - pharmacology
Oligonucleotide Array Sequence Analysis
Peripheral blood
Side effects
sirolimus
Sirolimus - analogs & derivatives
Sirolimus - pharmacology
Tacrolimus
Tacrolimus - pharmacology
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Summary:Following organ transplantation many patients suffer from drug-related side effects, or receive more immunosuppression than necessary to prevent rejection. Hence, parameters are needed to tailor the immunosuppressive therapy to the individual needs of an organ recipient. The aim of this study was to determine whether drug combinations provoke specific gene expression patterns in a simple assay system in vitro. Stimulated peripheral blood lymphocytes were cultured in the presence of cyclosporine A, tacrolimus, mycophenolic acid, everolimus and sirolimus, or combinations thereof. Using a cDNA microarray, we found that all samples clustered in drug-specific groups. Gene expression profiles were almost identical in PBL treated with either cyclosporine A or tacrolimus, and with either sirolimus or everolimus. More than 50 genes were synergistically affected by combinations of calcineurin-inhibitors and TOR-inhibitors and drug-specific regulated genes could be identified for both substance groups. Our data suggest that in vitro gene profiling can be used to describe synergistic effects of immunosuppressive drugs. Furthermore, our approach may help to identify marker genes urgently needed to optimize and individualize immunosuppressive drug regimens after organ transplantation.
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ISSN:0892-3973
1532-2513
DOI:10.1080/08923970802626268