Suurväli J, Pahtma M, Saar R, Paalme V, Nutt A, Tiivel T, Saaremäe M, Fitting C, Cavaillon J M, Rüütel Boudinot S
Department of Gene Technology, Tallinn University of Technology, Tallinn, Estonia.
Scand J Immunol. 2015 Jan;81(1):23-30. doi: 10.1111/sji.12250.
Immune cells express powerful and harmful effectors that require tight regulation. Heterotrimeric G proteins are critical mediators in translating extracellular signals into cell responses, which need a fine-tuned regulation for the control of cell activation. Regulator of G-protein signalling 16 (RGS16) has been identified as a key factor of G protein-mediated activation in lymphocytes, modulating inflammatory and survival responses of various cell types. However, data about the expression of this regulatory protein in monocytes are scarce, and it has remained unclear whether activation and migration of these cells are regulated by RGS16. In this study, the impact of RGS16 on the production of inflammatory cytokines by activated human monocytes was investigated in vitro using the human promonocytic cell line THP-1 as a model. Gain and loss of function experiments showed that RGS16 overexpression reduces the expression of pro-inflammatory cytokines IL-1β, IL-6, IL-8 and TNFα, while RGS16 knockdown by RNAi upregulates IL-1β, IL-6 and TNFα but not IL-8. RGS16 knockdown was also shown to enhance Pam3-mediated induction of the anti-inflammatory cytokine IL-10. Our results indicate that RGS16 restricts the activation-induced pro-inflammatory profile in myeloid cells.
免疫细胞表达需要严格调控的强大且有害的效应分子。异源三聚体G蛋白是将细胞外信号转化为细胞反应的关键介质，其需要精细调控以控制细胞活化。G蛋白信号调节因子16（RGS16）已被确定为淋巴细胞中G蛋白介导的活化的关键因子，可调节各种细胞类型的炎症和存活反应。然而，关于这种调节蛋白在单核细胞中的表达数据很少，并且这些细胞的活化和迁移是否受RGS16调节仍不清楚。在本研究中，以人原单核细胞系THP-1为模型，在体外研究了RGS16对活化的人单核细胞产生炎性细胞因子的影响。功能获得和缺失实验表明，RGS16过表达降低促炎细胞因子IL-1β、IL-6、IL-8和TNFα的表达，而RNAi敲低RGS16则上调IL-1β、IL-6和TNFα，但不上调IL-8。还显示RGS16敲低增强Pam3介导的抗炎细胞因子IL-10的诱导。我们的结果表明，RGS16限制了髓样细胞中活化诱导的促炎特征。
