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

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.