Biology Reference
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pathology and inflammation. By using bone marrow chimera mice, the same
group was able to show expression of
b
-arrestin 2 in eosinophilic and lym-
phocytic cells contributes to airway inflammation, while expression of
b
-arrestin 2 in structural cells contributes to airway hyperresponsiveness.
66
Another study investigated the role of
b
-arrestin 2 in CD4
þ
T lymphocytes
and found that
b
-arrestin 2 regulated IL-4 production and GATA3
expression.
47
b
-Arrestins can regulate
b
-agonist-induced desensitization of airway
smooth muscle
b
2ARs, which is the cause of loss of bronchoprotective
effect and deterioration of asthma control by
b
-agonists.
b
-Arrestin-2-
deficient mice show augmented
b
-agonist-mediated airway smooth muscle
relaxation and increased
b
-agonist-stimulated cyclic adenosine monop-
hosphate production. Knockdown of
b
-arrestins in cultured human airway
smooth muscle cells produced increased
b
-agonist-stimulated cyclic adeno-
sine monophosphate production. Collectively, these studies suggest that
b
-arrestins
regulate
b
2AR signaling and function in airway smooth
muscle.
160-162
IL-17 is a proinflammatory cytokine that plays a critical role in the path-
ogenesis of allergic asthma. A recent study found that
b
-arrestin 2 and IL-17
expression in CD4
þ
T cells from a murine asthma model were increased
compared with those from wild-type mice.
64
Moreover,
b
-arrestin 2 stim-
ulated IL-17 production and expression of CD4
þ
T lymphocytes in a
murine asthma model.
64
6.8. Cystic fibrosis
b
-Arrestin 2 protein level is increased in cystic fibrosis cell models,
Cftr
/
mouse nasal epithelia, and nasal scrapes obtained from cystic fibrosis
patients.
163
Elevated
b
-arrestin 2 expression leads to increased cAMP
response element-binding protein (CREB) activation and ERK activation
in
b
arr2-GFP expressing tracheal epithelial cells. Inhibition of ERK resulted
in diminished cAMP response element activation in both cells with
and without
b
arr2-GFP expression. Nasal epithelium excised from
Cftr
and
b
-arrestin 2 double knockout mice exhibit reduced pCREB and
pERK levels compared with
Cftr
/
mice, but similar to WT mice. Thus,
b
-arrestin 2 directly regulates cystic fibrosis-induced CREB activation
through the ERK signaling pathway.
164
6.9. Cardioprotection
In addition to regulating the PKA-apoptosis pathway,
b
1AR activa-
tion also signals through the
b
-arrestin-Src-MMP pathway, leading to
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