title: Influence of resveratrol on rheumatoid fibroblast-like synoviocytes analysed with gene chip transcription.
abstract: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that primarily attacks joints and is therefore a common cause of chronic disability and articular destruction. The hyperplastic growth of RA-fibroblast-like synoviocytes (FLSs) and their resistance against apoptosis are considered pathological hallmarks of RA. The natural antioxidant resveratrol is known for its antiproliferative and pro-apoptotic properties. This study investigated the effect of resveratrol on RA-FLS. RA-FLS were isolated from the synovium of 10 RA patients undergoing synovectomy or joint replacement surgery. RA-FLS were first stressed by pre-incubation with interleukin 1beta (IL-1β) and then treated with 100 μM resveratrol for 24h. In order to evaluate the influence of resveratrol on the transcription of genes, a Gene Chip Human Gene 1.0 ST Array was applied. In addition, the effect of dexamethasone on proliferation and apoptosis of RA-FLS was compared with that of resveratrol. Gene array analysis showed highly significant effects of resveratrol on the expression of genes involved in mitosis, cell cycle, chromosome segregation and apoptosis. qRT-PCR, caspase-3/7 and proliferation assays confirmed the results of gene array analysis. In comparison, dexamethasone showed little to no effect on reducing cell proliferation and apoptosis. Our in vitro findings point towards resveratrol as a promising new therapeutic approach for local intra-articular application against RA, and further clinical studies will be necessary.
authors.affiliation: Department of Orthopaedic Surgery, Medical University of Graz, Graz, Austria.
authors.forename: Mathias
authors.initials: M
authors.lastname: Glehr
authors.forename: Margherita
authors.initials: M
authors.lastname: Fritsch-Breisach
authors.forename: Birgit
authors.initials: B
authors.lastname: Lohberger
authors.forename: Sonja Maria
authors.initials: SM
authors.lastname: Walzer
authors.forename: Florentine
authors.initials: F
authors.lastname: Moazedi-Fuerst
authors.forename: Beate
authors.initials: B
authors.lastname: Rinner
authors.forename: Gerald
authors.initials: G
authors.lastname: Gruber
authors.forename: Winfried
authors.initials: W
authors.lastname: Graninger
authors.forename: Andreas
authors.initials: A
authors.lastname: Leithner
authors.forename: Reinhard
authors.initials: R
authors.lastname: Windhager
mesh_terms: D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D008517:Phytotherapy; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D013267:Stilbenes; D003907:Dexamethasone; D053148:Caspase 3; D053179:Caspase 7; D000077185:Resveratrol