Abstract

BackgroundInterleukin 17 (IL-17) is a proinflammatory cytokine produced by a new subset of activated CD4+ T cells, Th17 cells. We previously showed that increased Th17 cell populations were presented in human medulloblastoma-infiltrating T cells and peripheral blood. In this study, we attempted to address the possible role of Th17 cells in the biologic activity of IL-17 for tumor control.MethodsWe grafted fresh surgically obtained medulloblastoma into syngeneic athymic nude/nude mice. We intrapertonially injected splenocyte and murine IL-17 in mice on the second day. The tumor volume and the life spans of the mice were measured. Meanwhile, the IL-17, IL-6, IL-23, Ccl2, Ccl20 and IFN-gamma expression in the tumors was also examined by real-time PCR, Western blot and enzyme-linked immunosorbent assay.ResultsWe found that medulloblastoma growth in IL-17-injected mice was significantly inhibited compared to the non-IL-17 treated mice. In contrast to the IL-17 antitumor activity observed in mice injected with splenocytes, we observed that IFN-gamma, IL-6, IL-23, Ccl2, and Ccl20 proteins were significantly increased in tumor tissues of mice injected with IL-17.ConclusionsThese experiments suggest that IL-17 may promote splenocyte antitumor activity in medulloblastoma. We postulate that IL-17’s antitumor activity may be related to the increased protein levels of IFN-gamma, IL-6, IL-23, Ccl2, and Ccl20.

Highlights

  • Interleukin 17 (IL-17) is a proinflammatory cytokine produced by a new subset of activated CD4+ T cells, Th17 cells

  • IL‐6 and IL‐23 were overexpressed in IL‐17‐treated mice Because IL-6 and IL-23 are cytokines closely related to IL-17, we examined the expression levels of IL-6 and IL-23 in the medulloblastoma xenografts by real-time PCR and Western blot to investigate the microenvironment changes induced by IL-17

  • In conclusion, we found that splenocytes might inhibit the growth rates of medulloblastomas that were transplanted into nude mice, and this inhibition might be enhanced by IL-17

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Summary

Introduction

Interleukin 17 (IL-17) is a proinflammatory cytokine produced by a new subset of activated CD4+ T cells, Th17 cells. We previously showed that increased Th17 cell populations were presented in human medulloblastoma-infiltrating T cells and peripheral blood. We attempted to address the possible role of Th17 cells in the biologic activity of IL-17 for tumor control. Medulloblastoma is a malignant tumor of the cerebellum and one of the most frequent malignant tumors in children. Medulloblastoma is usually associated with a worse prognosis than other pediatric tumors. It is the most common malignant pediatric brain tumor. The median age of children at diagnosis is 5-year old, and the tumor age range extends into young adulthood.

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