IL-11-induced reduction of C/EBP transcription factor binding may contribute to the IL-12 downregulation in tumor-bearing mice

  • Authors:
    • Marta Torroella-Kouri
    • James C. Keith
    • Milena Ivanova
    • Diana M. Lopez
  • View Affiliations

  • Published online on: February 1, 2003     https://doi.org/10.3892/ijo.22.2.439
  • Pages: 439-448
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Abstract

Using a mammary tumor model syngeneic to BALB/c mice, we have characterized several tumor-derived factors. We now report that the DA-3 cell line derived from this tumor, as well as the in vivo tumor itself, express IL-11. The expression of IL-11 in the tumor is detectable at the transcriptional and translational levels, as evidenced by RT-PCR and Western blots. Using a murine IL-11 ELISA, we observed no differences in IL-11 production between normal and tumor-bearer's macrophages or T cells, with or without activation. Interestingly, elevated levels of IL-11 were found in the sera of tumor-bearers, when compared to normal animals and even higher levels of IL-11 were detected in the tumor cystic fluid. Macrophages from mice bearing large mammary tumors show an impaired production of IL-12 and NO, whereas T cells from the same animals display a deficient production of IFN-γ. Pretreatment of normal macrophages with IL-11 resulted in no decrease in NO production, nor an impaired production of IFN-γ was observed in normal T cells upon pretreatment with IL-11. However, pretreatment of normal macrophages with IL-11 resulted in a decreased production of IL-12, as revealed by ELISA and RT-PCR. Electromobility shift assays showed decreased binding of the transcription factor C/EBP to the IL-12p40 promoter of LPS-activated macrophages from normal animals, upon pretreatment with IL-11. In contrast, no differences were observed in the levels of NFκB binding under the same experimental conditions. Our results suggest that tumor-derived IL-11 may play a role in the depressed IL-12 production by macrophages, leading to the impaired immune functions observed during mammary tumorigenesis.

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February 2003
Volume 22 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Torroella-Kouri M, Keith JC, Ivanova M and Lopez DM: IL-11-induced reduction of C/EBP transcription factor binding may contribute to the IL-12 downregulation in tumor-bearing mice. Int J Oncol 22: 439-448, 2003
APA
Torroella-Kouri, M., Keith, J.C., Ivanova, M., & Lopez, D.M. (2003). IL-11-induced reduction of C/EBP transcription factor binding may contribute to the IL-12 downregulation in tumor-bearing mice. International Journal of Oncology, 22, 439-448. https://doi.org/10.3892/ijo.22.2.439
MLA
Torroella-Kouri, M., Keith, J. C., Ivanova, M., Lopez, D. M."IL-11-induced reduction of C/EBP transcription factor binding may contribute to the IL-12 downregulation in tumor-bearing mice". International Journal of Oncology 22.2 (2003): 439-448.
Chicago
Torroella-Kouri, M., Keith, J. C., Ivanova, M., Lopez, D. M."IL-11-induced reduction of C/EBP transcription factor binding may contribute to the IL-12 downregulation in tumor-bearing mice". International Journal of Oncology 22, no. 2 (2003): 439-448. https://doi.org/10.3892/ijo.22.2.439