Publication: Inhibition of the TWEAK/Fn14 pathway attenuates autoimmune arthritis in a SKG mouse model
Authors
Park, Jin Sil ; Kim, Sung Min ; Jung, Kyung Ah ; Lee, Jennifer ; Kwok, Seung Ki ; Cho, Mi La ; Park, Sung Hwan
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Publisher
Universidad de Murcia. Departamento de BiologĂa Celular e HistologĂa
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DOI
DOI: 10.14670/HH-11-813
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info:eu-repo/semantics/article
Description
Abstract
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.
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Citation
Histology and Histopathology, Vol.32, nÂş5, (2017)
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