Ectopic expression of interleukin-1 receptor type II enhances cell migration through activation of the pre-interleukin lot pathway

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-1 0 signaling but increased expression of the precursor form of IL-1 alpha (pIL-1 alpha) and its downstream targets, including interleukin 6 (IL-6), interleukin 8 (IL-8), and type I collagen alpha 1 (COL1A1). However, depleting gene expression using small RNA interference specific to either pIL-1 alpha 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 I (SIP-I) 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-1 alpha pathway to enhance cell migration. (C) 2008 Elsevier Ltd. All rights reserved.