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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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