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

• Published in: Histology and histopathology Vol. 32; no. 5; p. 481
• Main Authors: Park, Jin-Sil, Kim, Sung-Min, Jung, Kyung-Ah, Lee, Jennifer, Kwok, Seung-Ki, Cho, Mi-La, Park, Sung-Hwan
• Format: Journal Article
• Language: English
• Published: Spain 01.05.2017
• Subjects: Animals; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - pathology; Cytokine TWEAK; Disease Models, Animal; Immunohistochemistry; Mice; Mice, Inbred BALB C; Mice, Mutant Strains; Receptors, Tumor Necrosis Factor - antagonists & inhibitors; Receptors, Tumor Necrosis Factor - immunology; Signal Transduction - immunology; Th17 Cells - immunology; Tumor Necrosis Factors - antagonists & inhibitors; Tumor Necrosis Factors - immunology; TWEAK Receptor
• ISSN: 1699-5848
• DOI: 10.14670/HH-11-813

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.