Biology Reference
In-Depth Information
inhibition of
b
-arrestin 2 could be a therapeutic strategy in
Cryptococcus
infections.
27
6.1.5 Viral responses
Reports suggest that
b
-arrestins mediate antiviral responses.
b
-Arrestin1accel-
erates STAT1 tyrosine dephosphorylationby recruitingT-cell protein tyrosine
phosphatase (TC45) and negatively regulates IFN-
g
-induced gene transcrip-
tion in IFN-
g
-induced cellular antiviral responses.
127
b
-Arrestin 1 knockdown
promotes the antiviral immune response in vesicular stomatitis virus-infected
cells.
127
b
-Arrestin 2 plays a negative role inHIV-1 gp120 and opioid-induced
lymphocyte cell death.
60
Increased or decreased
b
-arrestin 2 expression
inhibited or enhanced gp120/morphine-induced apoptosis, respectively.
60
b
-Arrestins 1 and 2 can function as both positive and negative regulators of
adenovirus-induced innate immune responses both
in vivo
and
in vitro
.
114
6.2. Fibrosis
The molecular mechanisms that control progressive tissue fibrosis remain
poorly understood. Idiopathic pulmonary fibrosis (IPF) is a progressive disease
and a major cause of morbidity and mortality. Progressive pulmonary fibrosis
results from numerous microinjuries to the alveolar epithelia that lead to
excessive fibroblast activity. Lung epithelial cell apoptosis is believed to be
responsible for the initiation of fibrogenesis.
b
-Arrestins are known to regulate
cell apoptosis (reviewed in Refs.
19,57,139
). Some GPCRs are reported to
have a role in lung epithelial apoptosis. For instance, angiotensin II receptors
are expressed by lung alveolar epithelial cells, and the interaction of angioten-
sin II with its receptors mediates alveolar epithelial cell apoptosis.
140,141
How-
ever, it is unclear whether
b
-arrestins mediate type II epithelial cell apoptosis
during lung fibrosis. During tissue injury, TGF-
b
is released by fibroblasts and
the epithelium. There is abundant evidence that TGF-
b
is critical for the pro-
gression of pulmonary fibrosis due to its role in regulating collagen synthesis,
fibroblast proliferation, apoptosis, and myofibroblast differentiation.
142-144
b
-Arrestin 2, but not
b
-arrestin 1, mediates endocytosis of the type II
TGF-
b
receptor/type III TGF-
b
receptor complex and downregulates
TGF-
b
signaling
128
and bone morphogenetic protein 2 signaling.
129
In a lung
fibrosis model, our initial findings suggest that deficiency in
b
-arrestins may
not affect TGF-
b
-induced matrix production.
131
Further detailed studies,
such as prolonged treatment with TGF-
b
, may shed some light on the
role of
b
-arrestins in TGF-
b
signaling in inflammatory and fibrotic diseases
(
Fig. 14.2
).
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