Dexamethasone Suppresses IL-33-exacerbated Malignant Phenotype of U87MG Glioblastoma Cells via NF-B and MAPK Signaling Pathways

Background Interleukin (IL)-33 is highly expressed in glioblastoma (GBM) and promotes tumor progression. Targeting IL-33 may be an effective strategy for the treatment of GBM. Dexamethasone (DEX) is a controversial drug routinely used clinically in GBM therapy. Whether DEX has an effect on IL-33 is unknown. This study aimed to investigate the effect of DEX on IL-33 and the molecular mechanisms involved. Methods U87MG cells were induced by tumor necrosis factor (TNF)-alpha to express IL-33 and then treated with DEX. The mRNA levels of IL-33, NF-kappa B p65, ERK1/2, and p38 were determined by real-time quantitative PCR. The expression of IL-33, IkB alpha (a specific inhibitor of NF-kappa B) and MKP-1 (a negative regulator of MAPK), as well as the phosphorylation of NF-kappa B, ERK1/2 and p38 MAPK, were detected by Western blotting. The secretion of IL-33 was measured by ELISA. The proliferation, migration and invasion of U87MG cells were detected by CCK8 and transwell assays, respectively. Results DEX significantly reduced TNF-alpha-induced production of IL-33 in U87MG cells, which was dependent on inhibiting the activation of the NF-kappa B, ERK1/2 and p38 MAPK signaling pathways, and was accompanied by the increased expression of IkB alpha but not MKP-1. Furthermore, the proliferation, migration and invasion of U87MG cells exacerbated by IL-33 were suppressed by DEX. Conclusion DEX inhibited the production and tumor-promoting function of IL-33. Whether DEX can benefit GBM patients remains controversial. Our results suggest that GBM patients with high IL-33 expression may benefit from DEX treatment and deserve further investigation.