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Reply to Chen

International Journal of Obesity volume 34, page 1229 (2010)Cite this article

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In a comment to our paper reporting an increase in the activity of the interleukin (IL)-23/IL-17 (Th17) cytokine axis in obese women,1 Chen2 suggests that IL-17 might have a role in the development of obesity-related cancer. This indeed seems to be a plausible assumption in light of the recent experimental evidence supporting the involvement of IL-17 signalling in carcinogenesis.2 In relation to this problem, one should also bear in mind the ability of IL-17 to stimulate production of nitric oxide (NO), a pleiotropic free radical with a complex role in tumour progression.3 In contrast to the anticancer effects of high NO amounts generated by activated macrophages or NO-releasing compounds, low levels of NO produced by tumour cells and/or surrounding stroma apparently promote tumour growth through vasodilatation and angiogenesis.3 Others and we have recently demonstrated that IL-17 can trigger the expression of inducible NO synthase and subsequent NO production in various cell types through Janus kinase/signal transducers and activators of transcription/interferon regulatory factor-1, mitogen-activated protein kinase/activator protein-1 and tumour necrosis factor receptor-associated factor/nuclear factor-κB signalling pathways.4 Interestingly, although readily activating inducible NO synthase in endothelial cells, fibroblasts, astrocytes and some tumour cell lines, IL-17 was completely unable to stimulate NO production in macrophages.4 In contrast, the activity of the IL-12/interferon-γ (Th1) cytokine axis, which apparently was not increased in obese women,1 has been regarded as crucial for stimulation of NO-dependent macrophage anticancer responses.4, 5 Therefore, it is conceivable to assume that a shift of balance between Th1 and Th17 responses towards the latter, as seen in obesity,1 could contribute to cancer progression through selective low-level inducible NO synthase activation in tumour and/or surrounding stromal cells. Such an assumption is consistent with the ability of IL-17 to promote tumour growth via stimulation of endothelial cell migration and up-regulation of pro-angiogenic factors in fibroblasts and cancer cells.6 It should be noted, however, that IL-17 has also been found to activate tumour-specific cytotoxic CD8+ T cells, thus restricting tumour growth in vivo.7 Although this suggests a complex, context-dependent role of IL-17 in cancer, its possible involvement in development and progression of obesity-related cancer, as suggested by Chen,2 seems worthy of further investigation.

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References

  1. Sumarac-Dumanovic M, Stevanovic D, Ljubic A, Jorga J, Simic M, Stamenkovic-Pejkovic D et al. Increased activity of interleukin-23/interleukin-17 proinflammatory axis in obese women. Int J Obes (London) 2009; 33: 151–156.

    Article  CAS  Google Scholar 

  2. Chen J . The IL-23/IL-17 axis may be important in obesity-associated cancer by way of the activation of multiple signal pathways. Int J Obes (London) 2010, advance online publication, 30 March 2010; doi:10.1038/ijo.2010.29.

    Article  CAS  Google Scholar 

  3. Xu W, Liu LZ, Loizidou M, Ahmed M, Charles IG . The role of nitric oxide in cancer. Cell Res 2002; 12: 311–320.

    Article  Google Scholar 

  4. Miljkovic D, Trajkovic V . Inducible nitric oxide synthase activation by interleukin-17. Cytokine Growth Factor Rev 2004; 15: 21–32.

    Article  CAS  Google Scholar 

  5. Weiss JM, Subleski JJ, Wigginton JM, Wiltrout RH . Immunotherapy of cancer by IL-12-based cytokine combinations. Expert Opin Biol Ther 2007; 7: 1705–1721.

    Article  CAS  Google Scholar 

  6. Numasaki M, Fukushi J, Ono M, Narula SK, Zavodny PJ, Kudo T et al. Interleukin-17 promotes angiogenesis and tumor growth. Blood 2003; 101: 2620–2627.

    Article  CAS  Google Scholar 

  7. Martin-Orozco N, Muranski P, Chung Y, Yang XO, Yamazaki T, Lu S et al. T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity 2009; 31: 787–798.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Physiology, School of Medicine, University of Belgrade, Belgrade, Serbia

    D Stevanovic

  2. Institute of Endocrinology, Diabetes and Diseases of Metabolism, School of Medicine, University of Belgrade, Belgrade, Serbia

    M Sumarac-Dumanovic & D Micic

  3. Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Belgrade, Serbia

    V Trajkovic

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  1. D Stevanovic
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  2. M Sumarac-Dumanovic
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  3. D Micic
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  4. V Trajkovic
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Correspondence to V Trajkovic.

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Stevanovic, D., Sumarac-Dumanovic, M., Micic, D. et al. Reply to Chen. Int J Obes 34, 1229 (2010). https://doi.org/10.1038/ijo.2010.67

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