Expression Of New Alarmin IL-33 In Glioma And Its Effect On Glioma Cell Invasion

Backgroud:Glioma is the most common primary tumor in the central nervous system (CNS) and malignant gliomas, which account for 70% of gliomas. Glioma are the most frequent and lethal cancers originating in the CNS with a high recurrence and mortality rate. Interleukin-33 (IL-33) is a novel member of the IL-1 superfamily and functions as a ligand for ST2, which is a member of the IL-1 receptor family. It can induce synthesis of chemokine and Th2-associated cytokine via activation of several intracellular signaling pathways, including nuclear factor-kappaB (NF-κB), P38, and extracellular signal-regulated kinases ERK1/2. IL-33 has been shown to be involved in the pathophysiology of many disease, such as obesity, asthma, and arthritis. The research work on IL-33 has been advancing very rapidly in recent years, especially closely to invasion of tumor cells. Chemokine secretion is a complex and tightly controlled process, and intracellular signaling pathways regulating secretion are often specifically tailored to each chemokine and cell type. It is not very clear whether IL 33 in gliomas can also activate the corresponding signaling pathways, and affect the development of glioma.Objective:To investigate the expression of IL-33 in human glioma, and the effect of IL-33 on the invasion of glioma cells.Methods:By real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) to detect the expression of IL-33 gene in glioma and normal brain tissue specimens. Using Western blot, immunohistochemical S-P method to detect the expression of IL-33 proteins in normal brain tissues and glioma tissues. The expression and localization of IL-33 in glioma cell lines was studied by immunofluorescence. Transwell assay was conducted to study the effect of IL-33 on invasion of glioma cells. Western blot was performed to investigate the change of NF-κB protein and p-NF-κB after IL-33 treatment.Results:qRT-PCR, Western blot and immunohistochemistry showed that the expression of IL-33 in glioma tissues was higher than normal brain tissues. Immunofluorescence localization in glioma cells indicated that IL-33 mainly expressed in the nucleus, and ST2 was predominantly located in the cell membrane. IL-33 enhanced glioma cells invasion in vitro, and increased the expression of NF-κB protein.Conclusions:IL-33 is over-expressed in glioma tissues, and promote the cell invasion of glioma. Therefore, the further study of the mechanisms of IL-33 has important clinical significance, which will provide a new direction for clinical diagnosis and treatment.