Chang Shih-Yu, Su Pei-Fen, Lee Te-Chang
Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan, ROC.
Cytokine. 2009 Jan;45(1):32-8. doi: 10.1016/j.cyto.2008.10.013. Epub 2008 Nov 20.
Expression of interleukin-1 receptor type II (IL1R2), a decoy receptor for pro-inflammatory interleukin 1 (IL-1), is enhanced by chronic exposure of the human uroepithelial cell line HUC-1 to arsenite. To explore the function of IL1R2, we ectopically expressed IL1R2 in HUC-1 cells. IL1R2 overexpression results in changes in cell morphology, actin rearrangement, and promoted cell migration. Ectopic expression of IL1R2 specifically blocked exogenous IL-1beta signaling but increased expression of the precursor form of IL-1alpha (pIL-1alpha) and its downstream targets, including interleukin 6 (IL-6), interleukin 8 (IL-8), and type I collagen alpha1 (COL1A1). However, depleting gene expression using small RNA interference specific to either pIL-1alpha or COL1A1, but not IL-6 or IL-8, significantly attenuated the migration of IL1R2-overexpressing cells. Furthermore, IL1R2 overexpression was associated with enhanced expression of Smad-interacting protein 1 (SIP-1) and reduced expression of E-cadherin. Because SIP-1 is a repressor of COL1A1-induced E-cadherin expression, the present results suggest that IL1R2 overexpression is likely through activation of the pIL-1alpha pathway to enhance cell migration.
促炎白细胞介素1（IL-1）的诱饵受体白细胞介素-1受体II型（IL1R2）的表达，会因人类尿路上皮细胞系HUC-1长期暴露于亚砷酸盐而增强。为了探究IL1R2的功能，我们在HUC-1细胞中异位表达了IL1R2。IL1R2的过表达导致细胞形态改变、肌动蛋白重排，并促进细胞迁移。IL1R2的异位表达特异性阻断了外源性IL-1β信号传导，但增加了IL-1α前体形式（pIL-1α）及其下游靶点的表达，包括白细胞介素6（IL-6）、白细胞介素8（IL-8）和I型胶原蛋白α1（COL1A1）。然而，使用针对pIL-1α或COL1A1而非IL-6或IL-8的小RNA干扰来耗尽基因表达，可显著减弱IL1R2过表达细胞的迁移。此外，IL1R2过表达与Smad相互作用蛋白1（SIP-1）表达增强和E-钙黏蛋白表达降低有关。由于SIP-1是COL1A1诱导的E-钙黏蛋白表达的抑制剂，目前的结果表明，IL1R2过表达可能是通过激活pIL-1α途径来增强细胞迁移。
