Differential influences of bucillamine and methotrexate on the generation of fibroblast-like cells from bone marrow CD34+ cells of rheumatoid arthritis patients
| Autor: | Shunsei Hirohata, Tamiko Yanagida, Hideki Yoshikawa, Tetsuya Tomita |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
Immunology CD34 Fluorescent Antibody Technique Arthritis Antigens CD34 Bone Marrow Cells Arthritis Rheumatoid Ilium Antigen medicine Humans Vimentin Immunology and Allergy Cysteine Aged Pharmacology business.industry Stem Cells Anti-Inflammatory Agents Non-Steroidal Bucillamine Fibroblasts Middle Aged medicine.disease In vitro Culture Media Methotrexate medicine.anatomical_structure Antirheumatic Agents Rheumatoid arthritis Cancer research Female Indicators and Reagents Bone marrow Matrix Metalloproteinase 1 business Immunosuppressive Agents medicine.drug |
| Zdroj: | International Immunopharmacology. 9:86-90 |
| ISSN: | 1567-5769 |
| DOI: | 10.1016/j.intimp.2008.10.007 |
| Popis: | We have recently demonstrated that bone marrow CD34+ cells from rheumatoid arthritis (RA) patients displayed abnormal capacities to respond to TNF-alpha and to differentiate into fibroblast-like cells producing MMP-1 (type B synoviocyte -like cells). The current study examined the effects of representative potent disease-modifying antirheumatic drugs, including bucillamine (BUC) and methotrexate (MTX) on the in vitro generation of fibroblast-like cells from RA bone marrow CD34+ cells. CD34+ cells purified from bone marrow specimens of 8 patients with active RA were cultured in the presence or absence of pharmacologically attainable concentrations of intramolecular disulfide form of bucillamine (BUC-ID, 3 microM), a major metabolite of BUC or MTX (20 nM). After incubation for 28 days, the generation of fibroblast-like cells was assessed under phase-contrast light microscopy and the concentrations of MMP-1 and VEGF in the culture supernatants were measured by ELISA. BUC-ID, but not MTX, significantly suppressed the generation of fibroblast-like cells from RA bone marrow CD34+ cells stimulated with SCF, GM-CSF and TNF-alpha (p=0.024 as determined by Wilcoxon signed rank test). Accordingly, BUC-ID, but not MTX, significantly suppressed the production of MMP-1 (p=0.017) and VEGF (p=0.017) by RA bone marrow CD34+ cells, without inhibition of beta2-microglobulin production. These results demonstrate that BUC-ID, but not MTX, is a potent inhibitor of differentiation of fibroblast-like cells from RA bone marrow CD34+ cells. Since MTX, but not BUC, has been previously shown to influence on type A synoviocytes, the data provide rationale of combination of BUC and MTX in the treatment of RA. |
| Databáze: | OpenAIRE |
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