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Titolo:
Methotrexate inhibits rheumatoid synovitis by inducing apoptosis
Autore:
Nakazawa, F; Matsuno, H; Yudoh, K; Katayama, R; Sawai, T; Uzuki, M; Kimura, T;
Indirizzi:
Toyama Med & Pharmaceut Univ, Dept Orthoped Surg, Toyama 9300194, Japan Toyama Med & Pharmaceut Univ Toyama Japan 9300194 Toyama 9300194, Japan Iwate Med Sch, Dept Pathol, Iwate, Japan Iwate Med Sch Iwate JapanIwate Med Sch, Dept Pathol, Iwate, Japan
Titolo Testata:
JOURNAL OF RHEUMATOLOGY
fascicolo: 8, volume: 28, anno: 2001,
pagine: 1800 - 1808
SICI:
0315-162X(200108)28:8<1800:MIRSBI>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
LOW-DOSE METHOTREXATE; IN-VIVO MODEL; CELL-DEATH; ARTHRITIS; DRUGS; MECHANISMS; INDUCTION; ANTIBODY; TISSUE;
Keywords:
methotrexate; rheumatoid arthritis; synovium; apoptosis; scid mouse;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Nakazawa, F Toyama Med & Pharmaceut Univ, Dept Orthoped Surg, 2630 Sugitani, Toyama 9300194, Japan Toyama Med & Pharmaceut Univ 2630 Sugitani ToyamaJapan 9300194
Citazione:
F. Nakazawa et al., "Methotrexate inhibits rheumatoid synovitis by inducing apoptosis", J RHEUMATOL, 28(8), 2001, pp. 1800-1808

Abstract

Objective. To clarify the pharmacological action of methotrexate (MTX) on the synovium of patients with rheumatoid arthritis (RA) using severe combined immunodeficient (SCID) mice in which human RA synovial tissue had been grafted (SCID-HuRAg). Methods. One month after engraftment of human RA tissue into SCID mice, MTX (0.3 mg/kg) was administered orally, then the appearance of apoptosis in the grafted tissue was examined by TdT mediated dUTP nick end labeling (TUNIEL) staining and electron microscopy at various time points after MTX administration. In cultured synovial cells, synovial apoptotic changes after MTX treatment were studied by agarose gel electrophoresis and flow cytometricanalysis. To compare the histological changes induced by MTX with those induced by other disease modifying antirheumatic drugs (DMARD) and a nonsteroidal antiinflamatory drug, histological examination of the grafted synovialtissues from SCID-HuRAg mice was conducted after 4 weeks of oral administration of MTX (0.3 mg/kg/week), salazosulfapyridine (30 mg/kg/day), auranofin (0.2 mg/kg/day), bucillamine (10 mg/kg/day), or indomethacin (2 mg/kg/day). Results. A significant decrease in the number of inflammatory cells was observed in the grafted synovial tissue of MTX treated SCID-HuRAg. A similar antiinflammatory effect was not observed with the other DMARD. Induction ofapoptosis was noted with MTX treatment but not with the others. The pro-apoptotic effect of MTX was also observed in synovial cell cultures. Conclusion. MTX induces apoptosis in RA synovium that, in turn, may contribute to its antiinflammatory effect on RA synovitis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 20:34:31