The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Tumor-Secreted Lactic Acid Promotes IL-23/IL-17 Proinflammatory Pathway
Abstract
IL-23 is a proinflammatory cytokine consisting of a p19 subunit and a p40 subunit that is shared with IL-12. IL-23 is overexpressed in and around tumor tissues, where it induces local inflammation and promotes tumor development. Many tumor cells produce large amounts of lactic acid by altering their glucose metabolism. In this study, we show that lactic acid secreted by tumor cells enhances the transcription of IL-23p19 and IL-23 production in monocytes/macrophages and in tumor-infiltrating immune cells that are stimulated with TLR2 and 4 ligands. DNA elements responsible for this enhancing activity of lactic acid were detected in a 2.7-kb 5′-flanking region of the human IL-23p19 gene. The effect of lactic acid was strictly regulated by extracellular pH. Furthermore, by inducing IL-23 overproduction, lactic acid facilitated the Ag-dependent secretion of proinflammatory cytokine IL-17 but not IFN-γ by TLR ligand-stimulated mouse splenocytes. Interestingly, this effect was observed even in the absence of TLR ligand stimulation. These results suggest that rather than just being a terminal metabolite, lactic acid is a proinflammatory mediator that is secreted by tumor cells to activate the IL-23/IL-17 proinflammatory pathway but not the Th1 pathway. Targeting the lactic acid-induced proinflammatory response may be a useful approach for treating cancer.
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Cites
Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H. L., & Kuchroo, V. K. (2006) · Nature · doi:10.1038/nature04753 · Cited by 6,992
Veldhoen, M., Hocking, R. J., Atkins, C. J., Locksley, R. M., & Stockinger, B. (2006) · Immunity · doi:10.1016/j.immuni.2006.01.001 · Cited by 3,605
Transforming growth factor-β induces development of the TH17 lineage
Mangan, P. R., Harrington, L. E., O'Quinn, D. B., Helms, W. S., Bullard, D. C., Elson, C. O., Hatton, R. D., Wahl, S. M., Schoeb, T. R., & Weaver, C. T. (2006) · Nature · doi:10.1038/nature04754 · Cited by 3,087
Th17: An Effector CD4 T Cell Lineage with Regulatory T Cell Ties
Weaver, C. T., Harrington, L. E., Mangan, P. R., Gavrieli, M., & Murphy, K. M. (2006) · Immunity · doi:10.1016/j.immuni.2006.06.002 · Cited by 1,422
IL-23 promotes tumour incidence and growth
Langowski, J. L., Zhang, X., Wu, L., Mattson, J. D., Chen, T., Smith, K., Basham, B., McClanahan, T., Kastelein, R. A., & Oft, M. (2006) · Nature · doi:10.1038/nature04808 · Cited by 1,018
Tumor-derived lactic acid modulates dendritic cell activation and antigen expression
Gottfried, E., Kunz-Schughart, L. A., Ebner, S., Mueller-Klieser, W., Hoves, S., Andreesen, R., Mackensen, A., & Kreutz, M. (2006) · Blood · doi:10.1182/blood-2005-05-1795 · Cited by 729
Saio, M., Radoja, S., Marino, M., & Frey, A. B. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.10.5583 · Cited by 157
Cited by
Immunity, Inflammation, and Cancer
Grivennikov, S. I., Greten, F. R., & Karin, M. (2010) · Cell · doi:10.1016/j.cell.2010.01.025 · Cited by 10,755
The Nature of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment
Kumar, V., Patel, S., Tcyganov, E., & Gabrilovich, D. I. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.01.004 · Cited by 2,008
LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells
Brand, A., Singer, K., Koehl, G. E., Kolitzus, M., Schoenhammer, G., Thiel, A., Matos, C., Bruss, C., Klobuch, S., Peter, K., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.011 · Cited by 2,039
Lactate in the Regulation of Tumor Microenvironment and Therapeutic Approaches
de la Cruz-López, K. G., Castro-Muñoz, L. J., Reyes-Hernández, D. O., García-Carrancá, A., & Manzo-Merino, J. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01143 · Cited by 940
“In addition, lactate produced by the tumor cell promotes the overexpression of IL-23, present in different types of tumors (colon, breast, stomach, melanoma) (156), the presence of this cytokine promotes expression of IL17, Matrix metalloprotease 9 (MMP-9), increases angiogenesis and reduces the infiltration of CD8 in…”
BackgroundLactate modulation of immune responses in inflammatory versus tumour microenvironments
Certo, M., Tsai, C.-H., Pucino, V., Ho, P.-C., & Mauro, C. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-020-0406-2 · Cited by 924
Metadata
- Authors
- Shime, H., Yabu, M., Akazawa, T., Kodama, K., Matsumoto, M., Seya, T., & Inoue, N.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-06-01
- Volume
- 180
- Issue
- 11
- Pages
- 7175-7183
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1560846896
- Cited by
- 285
- References
- 7
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- closed
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- Shime, H., Yabu, M., Akazawa, T., Kodama, K., Matsumoto, M., Seya, T., & Inoue, N. (2008). Tumor-Secreted Lactic Acid Promotes IL-23/IL-17 Proinflammatory Pathway. The Journal of Immunology. https://doi.org/10.4049/jimmunol.180.11.7175
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