β-arrestin2 Stimulates Interleukin-17 Production and Expression of CD4+ T Lymphocytes in a Murine Asthma Model
-
Yi Liu
,
Gu-yi Wang
,
Shao-kun Liu
,
Mu-yi Yang
,
Li-bing Ma
,
Keng Li
,
Su-bo Gong
,
Li Zhang
,
Ping Chen
,
Xu-dong Xiang
Abstract
Allergic asthma is a complex and chronic inflammatory airway disease. Interleukin-17 is a pro-inflammatory cytokine which plays critical role in the pathogenesis of allergic asthma. It has been reported that β-arrestin2 regulated the development of allergic asthma at a proximal step in the inflammatory cascade. In this study, the influence of β-arrestin2 on Interleukin-17 production and expression of CD4+ T lymphocytes in a murine asthma model was investigated.
Splenic CD4+ T lymphocytes from wild-type mice and those from a murine asthma model were purified. CD4+ T lymphocytes from a murine asthma model were transfected with siRNAs targeting the β-arrestin2 or were pretreated with the ERK1/2 inhibitor,PD98059. After stimulation, the protein expression of β-arrestin2、phosphorylated- ERK1/2 and IL-17 were detection by Western blot; the mRNA expression of IL-17 were detected by real-time PCR; the accumulation of IL-17 in supernatants were detected by ELISA.
We found that β-arrestin2、phosphorylated-ERK1/2 and IL-17 expression in CD4+ T lymphocytes from a murine asthma model was increased compared with those from wild- type mice(p<0.01). Treatment of CD4+ T lymphocytes with siRNAs targeting the β-arrestin2 down-regulated phosphorylated- ERK 1/2 and IL-17 expression (p < 0.01). PD98059 decreased IL-17 production and expression in CD4+ T lymphocytes in a murine asthma model (p < 0.05).
We conclude that β-arrestin2 stimulated IL-17 production and expression of CD4+ T lymphocytes in a murine asthma model. The effect was partly mediated by ERK 1/2 activation. Targeting β-arrestin2 biological activity could be a valid therapeutic approach for the treatment of allergic asthma.
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| Issue | Vol 10, No 3 (2011) | |
| Section | Articles | |
| Keywords | ||
| Asthma β-arrestin2 CD4 T Lymphocytes Extracellular Signal-regulated Kinase 1/2 Interleukin-17 | ||
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