Abstract 5006: Interleukin-1 receptor type II regulates matrix metalloproteinases expression and plays oncogenic roles in HaCaT cells

Abstract

Abstract Interleukin-1 receptor type II (IL1R2) is an IL-1 decoy receptor, which plays a role to inhibit exogenous IL-1 signaling. Intriguingly, IL1R2 also performs as a pro- inflammatory factor via activation of intracellular IL-1α signaling in a variety of cells. In our previous study, we reported that long term arsenic exposure resulted in increased IL1R2 expression which led to increased motility of human urothelial cells. In the present study, we similarly found that the expression of IL1R2 was increased in long-term arsenic exposed HaCaT cells (A1, A2) and the tumorigenic derivative, T4R2 cells. Since matrix metalloproteinases (MMPs) are frequently increased in a variety of malignant tissues including skin cancer, we also revealed that a positive association of IL1R2 and MMP1 and MMP7 at either mRNA or protein levels, which were analyzed by quantitative real time RT-PCR and western blotting, respectively. To reveal the involvement of IL1R2 in up-regulation of MMPs, we adopted shRNA technique to silence the expression of IL1R2 in T4R2 cells. Our results demonstrated that MMP1 and MMP7 were suppressed in IL1R2 silencing T4R2 cells. Meanwhile, we found the enhanced expression of MMP1 and MMP7 in HaCaT cells with ectopically expressed IL1R2. Furthermore, we confirmed our previous finding showing that IL1R2 overexpression was accompanied with increased expression of precursor form of IL-1α protein (preIL-1α). Immunofluorescence staining showed the colocalization of IL1R2 and preIL-1α in the nucleus. In a xenograft mouse model, we found that HaCaT cells with ectopical expression of IL1R2 formed tumor in nude mice whereas IL1R2 silencing in T4R2 cells suppressed the tumorigenicity. Taken together, these results implicate that IL1R2 plays an oncogenic role in human keratinocyte transformation by upregulation of MMPs expression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5006. doi:10.1158/1538-7445.AM2011-5006