title: β-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 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 were 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.
authors: Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
authors: Yi
authors: Y
authors: Liu
authors: Gu-Yi
authors: GY
authors: Wang
authors: Shao-Kun
authors: SK
authors: Liu
authors: Mu-Yi
authors: MY
authors: Yang
authors: Li-Bing
authors: LB
authors: Ma
authors: Keng
authors: K
authors: Li
authors: Su-Bo
authors: SB
authors: Gong
authors: Li
authors: L
authors: Zhang
authors: Ping
authors: P
authors: Chen
authors: Xu-Dong
authors: XD
authors: Xiang
mesh_terms: D000818:Animals; D019390:Arrestins / Q000276:immunology* / Q000378:metabolism; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D019950:Mitogen-Activated Protein Kinase 1 / Q000276:immunology / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000276:immunology / Q000378:metabolism; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D020381:Interleukin-17; D000071557:beta-Arrestins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3