Iranian Journal of Allergy, Asthma and Immunology 2011. 10(3):171-182.

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.


Keywords


Asthma; β-arrestin2; CD4+ T Lymphocytes; Extracellular Signal-regulated Kinase 1/2; Interleukin-17

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References


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