Gene Expression Profiling of Rheumatoid Arthritis Synovial Cells Treated with Antirheumatic DrugsTissue Engineering Laboratory Department of Rheumatology Charité-Universitätsmedizin Berlin, Campus Mitte Tucholskystrasse 2 10117 Berlin, Germany
Tissue Engineering Laboratory Department of Rheumatology Charité-Universitätsmedizin Berlin, Campus Mitte Tucholskystrasse 2 10117 Berlin, Germany
Tissue Engineering Laboratory Department of Rheumatology Charité-Universitätsmedizin Berlin, Campus Mitte Tucholskystrasse 2 10117 Berlin, Germany
Tissue Engineering Laboratory Department of Rheumatology Charité-Universitätsmedizin Berlin, Campus Mitte Tucholskystrasse 2 10117 Berlin, Germany
Tissue Engineering Laboratory Department of Rheumatology Charité-Universitätsmedizin Berlin, Campus Mitte Tucholskystrasse 2 10117 Berlin, Germany
Tissue Engineering Laboratory Department of Rheumatology Charité-Universitätsmedizin Berlin, Campus Mitte Tucholskystrasse 2 10117 Berlin, Germany
Tissue Engineering Laboratory Department of Rheumatology Charité-Universitätsmedizin Berlin, Campus Mitte Tucholskystrasse 2 10117 Berlin, Germany
Tissue Engineering Laboratory Department of Rheumatology Charité-Universitätsmedizin Berlin, Campus Mitte Tucholskystrasse 2 10117 Berlin, Germany, TransTissue Technologies GmbH, Berlin, Germany
Nonbiological therapeutics are frequently used for the treatment of patients with rheumatoid arthritis (RA). Because the mechanisms of action of these therapeutics are unclear, the authors aimed to elucidate the molecular effects of typical antirheumatic drugs on the expression profile of RA-related genes expressed in activated synovial fibroblasts. For reasons of standardization and comparability, immortalized synovial fibroblasts derived from RA (RASF) and normal donors (NDSF) were treated with methotrexate, prednisolone, or diclofenac and used for gene expression profiling with oligonucleotide microarrays. The cytotoxicity of the antirheumatic drugs was tested in different concentrations by MTS tetrazolium assay. Genes that were differentially expressed in RASF compared to NDSF and reverted by treatment with antirheumatic drugs were verified by semiquantitative polymerase chain reaction and by chemiluminescent enzyme immunoassay. Treatment with methotrexate resulted in the reversion of the RA-related expression profile of genes associated with growth and apoptosis including insulin-like growth factor binding protein 3, retinoic acid induced 3, and caveolin 2 as well as in the re-expression of the cell adhesion molecule integrin
Key Words: synovial fibroblast • rheumatoid arthritis • drug screening • microarray
This version was published on April
1, 2007 Journal of Biomolecular Screening, Vol. 12, No. 3,
328-340 (2007) This article has been cited by other articles:
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6. Prednisolone reverted the RA-related profile of genes that are known from inflammation and suppressed interleukins 1ß and 8. Low or high doses of diclofenac had no effect on the expression profile of genes related to RA in synovial fibroblasts. These data give the first insight into the mechanisms of action of common antirheumatic drugs used for the treatment of arthritides. Synovial fibroblasts reflect the disease-related pathophysiology and are useful tools for screening putative antirheumatic compounds. (Journal of Biomolecular Screening 2007:328-340) 
