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Stat3 as a potential therapeutic target for rheumatoid arthritis

Rheumatoid arthritis (RA) is a multi-factorial disease characterized by chronic inflammation and destruction of multiple joints. To date, various biologic treatments for RA such as anti-tumor necrosis factor alpha antibodies have been developed; however, mechanisms underlying RA development remain u...

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Detalles Bibliográficos
Autores principales: Oike, Takatsugu, Sato, Yuiko, Kobayashi, Tami, Miyamoto, Kana, Nakamura, Satoshi, Kaneko, Yosuke, Kobayashi, Shu, Harato, Kengo, Saya, Hideyuki, Matsumoto, Morio, Nakamura, Masaya, Niki, Yasuo, Miyamoto, Takeshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591217/
https://www.ncbi.nlm.nih.gov/pubmed/28887478
http://dx.doi.org/10.1038/s41598-017-11233-w
Descripción
Sumario:Rheumatoid arthritis (RA) is a multi-factorial disease characterized by chronic inflammation and destruction of multiple joints. To date, various biologic treatments for RA such as anti-tumor necrosis factor alpha antibodies have been developed; however, mechanisms underlying RA development remain unclear and targeted therapy for this condition has not been established. Here, we provide evidence that signal transducer and activator of transcription 3 (Stat3) promotes inflammation and joint erosion in a mouse model of arthritis. Stat3 global KO mice show early embryonic lethality; thus, we generated viable Stat3 conditional knockout adult mice and found that they were significantly resistant to collagen-induced arthritis (CIA), the most common RA model, compared with controls. We then used an in vitro culture system to screen ninety-six existing drugs to select Stat3 inhibitors and selected five candidate inhibitors. Among them, three significantly inhibited development of arthritis and joint erosion in CIA wild-type mice. These findings suggest that Stat3 inhibitors may serve as promising drugs for RA therapy.