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Silencing
b
-arrestin 2 with specific siRNA reduced IL-17 expression.
64
Overexpression of
b
-arrestin 1 increased IL-17 expression, possibly by
acetylation of histone H4 in the promoter region of IL-17.
59
It would
be interesting to determine if
b
-arrestins have any role in activation of
Th17 cells.
4.
b
-ARRESTINS AND STRUCTURAL CELLS
b
-Arrestins
cells,
65,66
are
expressed in epithelial
endothelial
cells,
22,67,68
and smooth muscle.
22
b
-Arrestin 1 has been found to be
expressed in human endothelial cells and smooth muscle cells.
22
In these
cells,
b
-arrestin 1 expression can be upregulated by cAMP-inducing agents
such as cholera toxin, forskolin, iloprost, and isoproterenol.
22
b
-Arrestins
mediate the infections of
Streptococcus pneumonia
67
and
Neisseria meningitidis
69
through interactions with endothelial cells.
b
-Arrestin 2 regulates
thrombin-PAR1 signaling in endothelial cell adhesion.
68
b
-Arrestin influences CXCL12-mediated epithelial cell migration.
CXCL12-stimulated cell migration is enhanced by CXCR7/CXCR4
coexpression in a
b
-arrestin-dependent manner.
65
In a CXCR4/
CXCR7-expressing MDA-MB-231 breast cancer epithelial cell line, inhi-
bition of
b
-arrestin using either siRNA knockdown or a dominant negative
mutant suppressed CXCL12-induced cell migration.
65
5.
b
-ARRESTINS REGULATE IMMUNE SIGNALING
PATHWAYS
5.1.
-Arrestins and chemokine receptors
Chemokines are a family of small cytokines secreted by immune cells and
inflammatory cells. Receptors for chemokines are typically seven-
transmembrane GPCRs. Binding of chemokines and their cognate receptors
regulate chemotaxis of leukocytes into inflammatory sites
70
and cytokine
release.
b
-Arrestins are recruited to the receptors and mediate receptor
desensitization and internalization (reviewed in Refs.
11,18,21,71
).
CXC chemokines are one of the main subfamilies of chemokines.
b
-Arrestins have been shown to mediate the internalization and desensiti-
zation of IL-8-induced CXCR1,
72,73
CXCR2,
36,73,74
b
and CXCL9- and
CXCL10-induced CXCR3.
75
b
-Arrestins regulate CXCR4 internalization
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