Ectopic expression of interleukin-1 receptor type II enhances cell migration through activation of the pre-interleukin 1alpha 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-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.
Chang
Shih-Yu
SY
Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan, ROC.
Su
Pei-Fen
PF
Lee
Te-Chang
TC
D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D048430:Cell Shape; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D053574:Receptors, Interleukin-1 Type II / Q000235:genetics / Q000378:metabolism*; D019459:Urothelium / Q000166:cytology / Q000378:metabolism
D015820:Cadherins; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D011498:Protein Precursors; D053574:Receptors, Interleukin-1 Type II