title: Effects of beta-arrestin 2 on cytokine production of CD4+ T lymphocytes of mice with allergic asthma.
abstract: Beta-arrestin 2 has been shown to participate in the pathogenesis of asthma by inducing Th2 cell migration to the lungs. Whether beta-arrestin 2 regulates cytokine production of CD4+ T cells is still unknown. The aim of the present study was to investigate the effect of beta-arrestin 2 on the cytokine production of CD4+ T lymphocytes and the mechanism involved in a mouse model for asthma. After silencing beta-arrestin 2 expression in CD4+ T lymphocytes from asthmatic mice by RNA interference (RNAi), the interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) levels in CD4+ T lymphocyte culture supernatants with or without terbutaline stimulation were determined. Cell-surface beta2 adrenergic receptor (beta2AR) as well as GATA3 expression of CD4+ T lymphocytes were also measured. CD4+ T lymphocytes of mice with allergic asthma expressed higher levels of beta-arrestin 2 on both mRNA and protein levels. beta-arrestin 2 RNAi decreased IL-4 (43.16%) and GATA3 (protein 77.21%, mRNA 62.98%) expression after terbutaline stimulation. Cell-surface beta2AR of CD4+ T lymphocytes decreased (15.27%) after terbutaline treatment, but recovered after beta-arrestin 2 RNAi down-modulation. These findings demonstrate that beta-arrestin 2 regulates IL-4 production and GATA3 expression of CD4+ T lymphocytes partly through the beta2AR signaling pathway in an allergic asthma model.
authors.affiliation: Department of Respiratory Medicine, the Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
authors.forename: Guyi
authors.initials: G
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Muyi
authors.initials: M
authors.lastname: Yang
authors.forename: Shaokun
authors.initials: S
authors.lastname: Liu
authors.forename: Libing
authors.initials: L
authors.lastname: Ma
authors.forename: Subo
authors.initials: S
authors.lastname: Gong
authors.forename: Keng
authors.initials: K
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Xudong
authors.initials: X
authors.lastname: Xiang
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D019390:Arrestins / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D001249:Asthma / Q000276:immunology*; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000096:biosynthesis / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D034741:RNA, Small Interfering / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013726:Terbutaline / Q000494:pharmacology; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; C000605258:Arrb2 protein, mouse; D019390:Arrestins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D034741:RNA, Small Interfering; D018343:Receptors, Adrenergic, beta-2; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D015847:Interleukin-4; D007371:Interferon-gamma; D013726:Terbutaline