[p38 MAP Kinase inhibitor].
Nihon Rinsho Meneki Gakkai Kaishi
; 30(5): 390-7, 2007 Oct.
Article
en Ja
| MEDLINE
| ID: mdl-17984579
ABSTRACT
FR167653 is a potent inhibitor of p38 MAP Kinase and inhibits TNF-alpha and IL-1beta production in inflammatory cells. In this study we investigated the effect of FR167653 on CIA. CIA rats were subcutaneously injected with FR167653 (32 mg/kg/day) starting on the day of the booster injection and after the onset of arthritis in the prophylactic and therapeutic treatment groups, respectively. The hind paw swelling, radiolographic and histologic scores, and osteoclast number were evaluated. Serum and tissue cytokine levels were assessed by ELISA. Flow cytometric analysis of T-lymphocytes from bone marrow was also performed. The effect of FR167653 on in vitro osteoclast formation induced by sRANKL and TNF-alpha was examined. Hind paw swelling occurred in CIA rats but not in the prophylactic treatment group. Therapeutic treatment also significantly reduced the paw swelling. The mean radiographic, histologic score, and osteoclast number of the treatment group were significantly lower than those of CIA rats without treatment. FR167653 treatment reduced serum TNF-alpha and IL-1beta levels, ankle IL-1beta concentration, and CD4-CD8a+ T-cell population in bone marrow. Furthermore, FR167653 inhibited the osteoclast-like cell differentiation induced by both sRANKL and TNF-alpha in vitro. FR167653 prevented the onset of arthritis in a prophylactic treatment model and suppresses the progression of joint destruction in a therapeutic treatment model, suggesting that p38 MAP Kinase is a potential therapeutic target for rheumatoid arthritis.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Artritis Reumatoide
/
Pirazoles
/
Piridinas
/
Antiinflamatorios no Esteroideos
/
Proteínas Quinasas p38 Activadas por Mitógenos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
Ja
Revista:
Nihon Rinsho Meneki Gakkai Kaishi
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2007
Tipo del documento:
Article