Interleukin-22 (IL-22) is an inflammatory cytokine mainly produced by activated Th17 and Th22 cells. The data presented here demonstrate that IL-22 induced the migration and invasion of papillary thyroid cancer (PTC) cells. MicroRNA expression analysis and functional studies indicated that IL-22-mediated migration and invasion is positively regulated by miR-595. Further mechanistic studies revealed that sex-determining region Y-box 17 (Sox17) is directly targeted by miR-595. We then demonstrated that IL-22 regulated migration and invasion of PTC cells via inhibiting Sox17 expression. Interestingly, in PTC cell lines and PTC tissues, expression of IL-22 and miR-595 was upregulated and Sox17 downregulated compared with normal thyroid, and their expression levels were closely correlated. Taken together, this present study suggests that IL-22 stimulation enhances the migration and invasion of PTC cells by regulating miR-595 and its target Sox17.

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Abstract. Interleukin (IL)-22 is newly identified proinflammatory cytokine involved in the T helper (Th)17 and Th22 response. However, the possible role of IL-22 in glioma remains uncertain. The results of the present study demonstrated higher expression levels of IL-22 and the receptor IL-22BP in the brain of GL261 glioma-inoculation mice, suggesting the regulatory role of IL-22 in glioma. Injection of IL-22 increased the severity of glioma in vivo and higher expression levels of IL-6, IL-1β and tumor necrosis factor (TNF)-α were detected in the brain using ELISA following IL-22 injection. To elucidate the mechanism underlying the effects of IL-22, the present study aimed firstly to determine the expression levels of IL-22 receptor in a glioma cell line via reverse transcription quantitative polymerase chain reaction. IL-22 treatment significantly increased the expression levels of signal transducer and activator of transcription (STAT)3 and the mRNA expression levels of STAT6 compared with the vehicle control. These results suggested that IL-22 may activate the Janus kinase (JAK)/STAT signaling pathway in glioma. Furthermore, IL-22 positively regulated the proliferation of glioma, consistent with its role in vivo. Conversely, IL-22-deficient mice exhibited prolonged survival compared with wild-type (WT) mice, and the expression levels of inflammatory cytokines were decreased in the brain of IL-22 knock-out (KO) mice compared with WT mice. Concordant with these results, it was observed that IL-22-neutralising antibody was able to increase the survival of mice with glioma and attenuate the disease by significantly reducing the cytokine levels in the brain. In conclusion, the results of the present study demonstrated that expression levels of IL-22 in the brain of mice with glioma may enhance symptoms due to the increased cytokine production of IL-6, IL-1β and TNF-α; this is consistent with IL-6/JAK/STAT signalling activation in vitro. Decreasing the expression levels of IL-22, achieved either with IL-22-KO mice or IL-22-neutralising antibody demonstrated protective effects on glioma development. Therefore, IL-22 may serve as a potential therapeutic target for glioma.

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