The inhibitory effect of disease-modifying anti-rheumatic drugs and steroids on gliostatin/platelet-derived endothelial cell growth factor production in human fibroblast-like synoviocytes.
Gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) is known to have both angiogenic and arthritogenic activities. The purpose of this study was to investigate whether disease-modifying anti-rheumatic drugs (DMARDs) and steroids are involved in the regulation of GLS expression. Fibroblast-like synoviocytes (FLSs) obtained from patients with rheumatoid arthritis (RA) were cultured and stimulated by interleukin (IL)-1beta with or without DMARDs and steroids. The expression levels of GLS were determined using the reverse transcription-polymerase chain reaction and an ELISA. In cultured rheumatoid FLSs, the expression of GLS mRNA was significantly increased by stimulation with IL-1beta. By contrast, GLS mRNA levels in IL-1beta-stimulated FLSs were reduced by treatment with aurothioglucose (AuTG) and dexamethasone (DEX). These findings indicate that AuTG and DEX have anti-rheumatic activity, which is mediated via the suppression of GLS production. Neither methotrexate (MTX) nor sulfasalazine (SSZ) had a significant influence on GLS levels in our study.
Department of Musculoskeletal Medicine, Nagoya City University Graduate School of Medical Sciences, Mizuho-Ku, Nagoya , 467-8601, Japan.
Takuma
T
Kusabe
Yuko
Y
Waguri-Nagaya
Tomohiro
T
Tanikawa
Mineyoshi
M
Aoyama
Muneyoshi
M
Fukuoka
Masaaki
M
Kobayashi
Takanobu
T
Otsuka
Kiyofumi
K
Asai
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000601:surgery; D002477:Cells / Q000378:metabolism; D002478:Cells, Cultured; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004550:Elbow; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007717:Knee; D008727:Methotrexate / Q000494:pharmacology; D008875:Middle Aged; D050607:Organogold Compounds / Q000494:pharmacology; D019637:Orthopedic Procedures; D010396:Penicillamine / Q000494:pharmacology; D010648:Phenylacetates / Q000494:pharmacology; D012460:Sulfasalazine / Q000494:pharmacology; D013583:Synovial Membrane / Q000378:metabolism*; D013939:Thymidine Phosphorylase / Q000032:analysis / Q000096:biosynthesis*
D000305:Adrenal Cortex Hormones; D018501:Antirheumatic Agents; D050607:Organogold Compounds; D010648:Phenylacetates; C052562:4-(acetylamino)benzeneacetic acid; D012460:Sulfasalazine; D003907:Dexamethasone; D013939:Thymidine Phosphorylase; D010396:Penicillamine; D003545:Cysteine; C026535:bucillamine; D008727:Methotrexate