Diminished PKC activity and decreased binding of transcription factors are involved in the impaired production of nitric oxide by macrophages from tumor-bearing mice

  • Authors:
    • Michael R. Di Napoli
    • Marta Torroella-Kouri
    • Giselle Perry
    • Diana M. Lopez
  • View Affiliations

  • Published online on: March 1, 2005     https://doi.org/10.3892/ijmm.15.3.503
  • Pages: 503-511
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Abstract

In previous studies we have shown that peritoneal macrophages (PEM) from mammary tumor-bearing BALB/c mice (T-PEM) display a diminished ability to lyse tumor cells upon stimulation with LPS, a phenomenon that is associated to a lower production of nitric oxide, and that is reverted upon costimulation with IFN-γ. The reduced lytic activity and NO production displayed by T-PEM upon LPS activation were earlier shown by us to be due to a diminished transcription of the inducible nitric oxide synthase (iNOS) gene. In the present study, we have investigated the participation of possible signaling molecules and transcription factors - PKC, NF-κB, C/EBP and IRF-1 - in the downregulation of NO production in LPS-activated T-PEM. It was found that PKC activity was greatly reduced in T-PEM as compared to normal macrophages, and did not respond to activation. Interestingly, the different PKC isozyme levels were not significantly altered in T-PEM, with the exception of PKC δ. Alterations in the binding activity of the transcription factors NF-κB and C/EBP appeared to be involved in the reduced transcription of iNOS previously observed in T-PEM after LPS activation. These results provide evidence that reductions in iNOS transcription secondary to alterations in cell signaling may be responsible for the diminished capacity of macrophages of LPS-activated tumor-bearers to produce NO and lyse tumor targets.

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March 2005
Volume 15 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Di Napoli MR, Torroella-Kouri M, Perry G and Lopez DM: Diminished PKC activity and decreased binding of transcription factors are involved in the impaired production of nitric oxide by macrophages from tumor-bearing mice. Int J Mol Med 15: 503-511, 2005
APA
Di Napoli, M.R., Torroella-Kouri, M., Perry, G., & Lopez, D.M. (2005). Diminished PKC activity and decreased binding of transcription factors are involved in the impaired production of nitric oxide by macrophages from tumor-bearing mice. International Journal of Molecular Medicine, 15, 503-511. https://doi.org/10.3892/ijmm.15.3.503
MLA
Di Napoli, M. R., Torroella-Kouri, M., Perry, G., Lopez, D. M."Diminished PKC activity and decreased binding of transcription factors are involved in the impaired production of nitric oxide by macrophages from tumor-bearing mice". International Journal of Molecular Medicine 15.3 (2005): 503-511.
Chicago
Di Napoli, M. R., Torroella-Kouri, M., Perry, G., Lopez, D. M."Diminished PKC activity and decreased binding of transcription factors are involved in the impaired production of nitric oxide by macrophages from tumor-bearing mice". International Journal of Molecular Medicine 15, no. 3 (2005): 503-511. https://doi.org/10.3892/ijmm.15.3.503