Beta-arrestin2 stimulates interleukin-17 production and expression of CD4+ T lymphocytes in a murine asthma model

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 beta-arrestin2 regulated the development of allergic asthma at a proximal step in the inflammatory cascade. In this study, the influence of beta-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 beta-arrestin2 or were pretreated with the ERK1/2 inhibitor, PD98059. After stimulation, the protein expression of beta-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 beta-arrestin2 phosphorylated-ERK1/2 and IL-17 expression in CD4+ T lymphocytes from a murine asthma model was increased compared with those from wildtype mice[p<0.01]. Treatment of CD4+ T lymphocytes with siRNAs targeting the beta-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 beta-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 beta-arrestin2 biological activity could be a valid therapeutic approach for the treatment of allergic asthma