IL-33 enhances glioma cell migration and invasion by upregulation of MMP2 and MMP9 via the ST2-NF-κB pathway

Abstract

As an important member of the interleukin (IL)-1 family, IL-33 plays a significant role in tumor progression. To explore this, we previously analyzed the association between IL-33 expression and the prognosis of patients with glioma. However, the function of the IL-33/ST2 axis in glioma remained unclear. In the present study, immunofluorescent staining results revealed that the expression levels of IL-33 and ST2 receptor in glioma tissues were higher than those in normal brain tissues. Invasion and migration assays demonstrated that IL-33 significantly increased glioma cell invasion and migration in vitro. Furthermore, knockdown of ST2 by siRNA attenuated the IL-33-induced increase in invasion and migration. In addition, ELISA results revealed that IL-33 upregulated the expression of matrix metalloproteinase (MMP)2 and MMP9. Western blot analysis results indicated that IL-33 stimulation increased the phosphorylation of nuclear factor-κB (NF-κB) in a time-And dose-dependent manner. Moreover, silencing of the NF-κB pathway by BAY 11-7082 resulted in the inhibition of IL-33- induced invasion and migration, as well as the downregulation of MMP2 and MMP9 production. These findings indicate that IL-33 may be involved in the process of glioma cell invasion and migration by upregulating MMP2 and MMP9 via the ST2-NF-κB signaling pathway. Thus, IL-33 may be a novel therapeutic target for glioma.