Inhibition of the TWEAK/Fn14 pathway attenuates autoimmune arthritis in a SKG mouse model

• Jin-Sil Park ^[1] ; Sung-Min Kim ^[1] ; Kyung-Ah Jung ^[1] ; Jennifer Lee ^[1] ; Seung-Ki Kwok ^[1] ; Mi-La Cho ^[1] ; Sung-Hwan Park ^[1]
  1. [1] Catholic University of Korea

     Catholic University of Korea

     Corea del Sur

     
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 32, Nº. 5, 2017, págs. 481-490
• Idioma: inglés
• Enlaces
  • Texto completo
• Resumen

  • Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a proinflammatory cytokine that is involved in pathogenesis of abnormal or disregulated inflammation. To verify how TWEAK/fibroblast growth factor-inducible gene 14 (Fn14) signals affect development of Th17 cells in arthritis, we utilized the SKG mouse, which spontaneously develops Th17-mediated autoimmune arthritis. Fn14-Fc was administered to zymosan A-induced arthritogenic SKG mice, and the effects in vivo were examined. Destruction of cartilage and bone damage was assessed by Hematoxylin and Eosin, and safranin O staining of the affected tissues. Phenotypic analysis of cells expressing inflammatory cytokines and angiogenesis-related factors, and the expression of transcription factor STAT3 in the affected joints were determined by immunohistochemistry. Blockade of Fn14 with Fn14-Fc reduced the clinical and histologic scores of inflammatory arthritis in the mouse model of spontaneously developed chronic autoimmune arthritis. Fn14-Fc suppressed production of inflammatory cytokines and angiogenesis-promoting factors, such as vascular endothelial growth factor and matrix metalloproteinase 3. Moreover, blocking of the TWEAK signal inhibited expression of STAT3 as well as interleukin-17 and -21 produced by Th17 cells. These results implicate TWEAK as a potential molecular target for treatment or prevention of inflammatory arthritis and autoimmune diseases such as rheumatoid arthritis