ecstatichamster
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http://onlinelibrary.wiley.com/stor...15&s=40bb76a22270d21539c6153ab1b8993aa96101c8
A naturally occurring TLR-4 antagonist,
highly purified lipopolysaccharide (LPS) from
Bartonella quintana, was first characterized using mouse
macrophages and human dendritic cells (DCs). Mice
with collagen-induced arthritis (CIA) and mice with
spontaneous arthritis caused by interleukin-1 receptor
antagonist (IL-1Ra) gene deficiency were treated with
TLR-4 antagonist.
The clinical score for joint inflammation,
histologic characteristics of arthritis, and local
expression of IL-1 in joints were evaluated after treatment.
Results. The TLR-4 antagonist inhibited DC maturation
induced by Escherichia coli LPS and cytokine
production induced by both exogenous and endogenous
TLR-4 ligands, while having no effect on these parameters
by itself.
Treatment of CIA using TLR-4 antagonist
substantially suppressed both clinical and histologic
characteristics of arthritis without influencing the
adaptive anti–type II collagen immunity crucial for this
model. Treatment with TLR-4 antagonist strongly reduced
IL-1 expression in articular chondrocytes and
synovial tissue. Furthermore, such treatment inhibited
IL-1–mediated autoimmune arthritis in IL-1Ra/ mice
and protected the mice against cartilage and bone
pathology.
Conclusion. In the present study, we demonstrate
for the first time that inhibition of TLR-4 suppresses the
severity of experimental arthritis and results in lower
IL-1 expression in arthritic joints. Our data suggest that
TLR-4 might be a novel target in the treatment of
rheumatoid arthritis.
Puzzling indeed.
A naturally occurring TLR-4 antagonist,
highly purified lipopolysaccharide (LPS) from
Bartonella quintana, was first characterized using mouse
macrophages and human dendritic cells (DCs). Mice
with collagen-induced arthritis (CIA) and mice with
spontaneous arthritis caused by interleukin-1 receptor
antagonist (IL-1Ra) gene deficiency were treated with
TLR-4 antagonist.
The clinical score for joint inflammation,
histologic characteristics of arthritis, and local
expression of IL-1 in joints were evaluated after treatment.
Results. The TLR-4 antagonist inhibited DC maturation
induced by Escherichia coli LPS and cytokine
production induced by both exogenous and endogenous
TLR-4 ligands, while having no effect on these parameters
by itself.
Treatment of CIA using TLR-4 antagonist
substantially suppressed both clinical and histologic
characteristics of arthritis without influencing the
adaptive anti–type II collagen immunity crucial for this
model. Treatment with TLR-4 antagonist strongly reduced
IL-1 expression in articular chondrocytes and
synovial tissue. Furthermore, such treatment inhibited
IL-1–mediated autoimmune arthritis in IL-1Ra/ mice
and protected the mice against cartilage and bone
pathology.
Conclusion. In the present study, we demonstrate
for the first time that inhibition of TLR-4 suppresses the
severity of experimental arthritis and results in lower
IL-1 expression in arthritic joints. Our data suggest that
TLR-4 might be a novel target in the treatment of
rheumatoid arthritis.
Puzzling indeed.
