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Article

The inflammatory cytokine IL‑22 promotes murine gliomas via proliferation

  • Authors:
    • Xiguo Liu
    • Junjing Yang
    • Wankai Deng
  • View Affiliations / Copyright

    Affiliations: Department of Head and Neck and Neurosurgery, Hubei Cancer Hospital, Wuhan, Hubei 430079, P.R. China
  • Pages: 1087-1092
    |
    Published online on: January 18, 2017
       https://doi.org/10.3892/etm.2017.4059
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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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1 

Yamanaka R, Abe T, Yajima N, Tsuchiya N, Homma J, Kobayashi T, Narita M, Takahashi M and Tanaka R: Vaccination of recurrent glioma patients with tumour lysate-pulsed dendritic cells elicits immune responses: Results of a clinical phase I/II trial. Br J Cancer. 89:1172–1179. 2003. View Article : Google Scholar : PubMed/NCBI

2 

Yu JS, Liu G, Ying H, Yong WH, Black KL and Wheeler CJ: Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma. Cancer Res. 64:4973–4979. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Liau LM, Prins RM, Kiertscher SM, Odesa SK, Kremen TJ, Giovannone AJ, Lin JW, Chute DJ, Mischel PS, Cloughesy TF and Roth MD: Dendritic cell vaccination in glioblastoma patients induces systemic and intracranial T-cell responses modulated by the local central nervous system tumor microenvironment. Clin Cancer Res. 11:5515–5525. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Valle RD, de Cerio AL, Inoges S, Tejada S, Pastor F, Villanueva H, Gallego J, Espinos J, Aristu J, Idoate MA, et al: Dendritic cell vaccination in glioblastoma after fluorescence-guided resection. World J Clin Oncol. 3:142–149. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Fabry Z, Raine CS and Hart MN: Nervous tissue as an immune compartment: The dialect of the immune response in the CNS. Immunol Today. 15:218–224. 1994. View Article : Google Scholar : PubMed/NCBI

6 

Carmen J, Gowing G, Julien JP and Kerr D: Altered immune response to CNS viral infection in mice with a conditional knock-down of macrophage-lineage cells. Glia. 54:71–80. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Andersson U and Tracey KJ: Neural reflexes in inflammation and immunity. J Exp Med. 209:1057–1068. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Palucka K and Banchereau J: Cancer immunotherapy via dendritic cells. Nat Rev Cancer. 12:265–277. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Almolda B, Costa M, Montoya M, Gonzàlez B and Castellano B: Increase in Th17 and T-reg lymphocytes and decrease of IL22 correlate with the recovery phase of acute EAE in rat. PloS One. 6:e274732011. View Article : Google Scholar : PubMed/NCBI

10 

Cheng F, Guo Z, Xu H, Yan D and Li Q: Decreased plasma IL22 levels, but not increased IL17 and IL23 levels, correlate with disease activity in patients with systemic lupus erythematosus. Ann Rheum Dis. 68:604–606. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Van Belle AB, de Heusch M, Lemaire MM, Hendrickx E, Warnier G, Dunussi-Joannopoulos K, Fouser LA, Renauld JC and Dumoutier L: IL-22 is required for imiquimod-induced psoriasiform skin inflammation in mice. J Immunol. 188:462–469. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Jiang R, Tan Z, Deng L, Chen Y, Xia Y, Gao Y, Wang X and Sun B: Interleukin-22 promotes human hepatocellular carcinoma by activation of STAT3. Hepatology. 54:900–909. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Lejeune D, Dumoutier L, Constantinescu S, Kruijer W, Schuringa JJ and Renauld JC: Interleukin-22 (IL-22) activates the JAK/STAT, ERK, JNK and p38 MAP kinase pathways in a rat hepatoma cell line. Pathways that are shared with and distinct from IL-10. J Biol Chem. 277:33676–33682. 2002. View Article : Google Scholar : PubMed/NCBI

14 

Zhang W, Chen Y, Wei H, Zheng C, Sun R, Zhang J and Tian Z: Antiapoptotic activity of autocrine interleukin-22 and therapeutic effects of interleukin-22-small interfering RNA on human lung cancer xenografts. Clin Cancer Res. 14:6432–6439. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Sabat R, Ouyang W and Wolk K: Therapeutic opportunities of the IL-22-IL-22R1 system. Nat Rev Drug Discov. 13:21–38. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Kreymborg K, Etzensperger R, Dumoutier L, Haak S, Rebollo A, Buch T, Heppner FL, Renauld JC and Becher B: IL-22 is expressed by Th17 cells in an IL-23-dependent fashion, but not required for the development of autoimmune encephalomyelitis. J Immunol. 179:8098–8104. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Backert I, Koralov SB, Wirtz S, Kitowski V, Billmeier U, Martini E, Hofmann K, Hildner K, Wittkopf N, Brecht K, et al: STAT3 activation in Th17 and Th22 cells controls IL-22-mediated epithelial host defense during infectious colitis. J Immunol. 193:3779–3791. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Davis FG and McCarthy BJ: Current epidemiological trends and surveillance issues in brain tumors. Expert Rev Anticancer Ther. 1:395–401. 2001. View Article : Google Scholar : PubMed/NCBI

19 

Colleoni F and Torrente Y: The new challenge of stem cell: Brain tumour therapy. Cancer Lett. 272:1–11. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD and Dirks PB: Identification of human brain tumour initiating cells. Nature. 432:396–401. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Silber J, Lim DA, Petritsch C, Persson AI, Maunakea AK, Yu M, Vandenberg SR, Ginzinger DG, James CD, Costello JF, et al: miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells. BMC Med. 6:142008. View Article : Google Scholar : PubMed/NCBI

22 

Wei J, Wang F, Kong LY, Xu S, Doucette T, Ferguson SD, Yang Y, McEnery K, Jethwa K, Gjyshi O, et al: MiR-124 inhibits STAT3 signaling to enhance T cell-mediated immune clearance of glioma. Cancer Res. 73:3913–3926. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Kaplan MH, Schindler U, Smiley ST and Grusby MJ: Stat6 is required for mediating responses to IL-4 and for development of Th2 cells. Immunity. 4:313–319. 1996. View Article : Google Scholar : PubMed/NCBI

24 

Monteleone G, Holloway J, Salvati VM, Pender SL, Fairclough PD, Croft N and MacDonald TT: Activated STAT4 and a functional role for IL-12 in human Peyer's patches. J Immunol. 170:300–307. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Morinobu A, Gadina M, Strober W, Visconti R, Fornace A, Montagna C, Feldman GM, Nishikomori R and O'Shea JJ: STAT4 serine phosphorylation is critical for IL-12-induced IFN-gamma production but not for cell proliferation. Proc Natl Acad Sci USA. 99:12281–12286. 2002. View Article : Google Scholar : PubMed/NCBI

26 

Sovran B, Loonen LM, Lu P, Hugenholtz F, Belzer C, Stolte EH, Boekschoten MV, van Baarlen P, Kleerebezem M, de Vos P, et al: IL-22-STAT3 pathway plays a key role in the maintenance of ileal homeostasis in mice lacking secreted mucus barrier. Inflamm Bowel Dis. 21:531–542. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Zhang L, Liu W, Alizadeh D, Zhao D, Farrukh O, Lin J, Badie SA and Badie B: S100B attenuates microglia activation in gliomas: Possible role of STAT3 pathway. Glia. 59:486–498. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Lo HW, Cao X, Zhu H and Ali-Osman F: Constitutively activated STAT3 frequently coexpresses with epidermal growth factor receptor in high-grade gliomas and targeting STAT3 sensitizes them to Iressa and alkylators. Clin Cancer Res. 14:6042–6054. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Zisakis A, Piperi C, Themistocleous MS, Korkolopoulou P, Boviatsis EI, Sakas DE, Patsouris E, Lea RW and Kalofoutis A: Comparative analysis of peripheral and localised cytokine secretion in glioblastoma patients. Cytokine. 39:99–105. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Suzumura A, Sawada M, Yamamoto H and Marunouchi T: Transforming growth factor-beta suppresses activation and proliferation of microglia in vitro. J Immunol. 151:2150–2158. 1993.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liu X, Yang J and Deng W: The inflammatory cytokine IL‑22 promotes murine gliomas via proliferation. Exp Ther Med 13: 1087-1092, 2017.
APA
Liu, X., Yang, J., & Deng, W. (2017). The inflammatory cytokine IL‑22 promotes murine gliomas via proliferation. Experimental and Therapeutic Medicine, 13, 1087-1092. https://doi.org/10.3892/etm.2017.4059
MLA
Liu, X., Yang, J., Deng, W."The inflammatory cytokine IL‑22 promotes murine gliomas via proliferation". Experimental and Therapeutic Medicine 13.3 (2017): 1087-1092.
Chicago
Liu, X., Yang, J., Deng, W."The inflammatory cytokine IL‑22 promotes murine gliomas via proliferation". Experimental and Therapeutic Medicine 13, no. 3 (2017): 1087-1092. https://doi.org/10.3892/etm.2017.4059
Copy and paste a formatted citation
x
Spandidos Publications style
Liu X, Yang J and Deng W: The inflammatory cytokine IL‑22 promotes murine gliomas via proliferation. Exp Ther Med 13: 1087-1092, 2017.
APA
Liu, X., Yang, J., & Deng, W. (2017). The inflammatory cytokine IL‑22 promotes murine gliomas via proliferation. Experimental and Therapeutic Medicine, 13, 1087-1092. https://doi.org/10.3892/etm.2017.4059
MLA
Liu, X., Yang, J., Deng, W."The inflammatory cytokine IL‑22 promotes murine gliomas via proliferation". Experimental and Therapeutic Medicine 13.3 (2017): 1087-1092.
Chicago
Liu, X., Yang, J., Deng, W."The inflammatory cytokine IL‑22 promotes murine gliomas via proliferation". Experimental and Therapeutic Medicine 13, no. 3 (2017): 1087-1092. https://doi.org/10.3892/etm.2017.4059
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