NF-kappaB activation mediates the response of a subpopulation of basal uroepithelial cells to a cell wall component of Enterococcus faecalis.

Academic Article

Abstract

  • Earlier in vitro studies revealed that treatment of basal urothelial cells (UT) with lipoteichoic acid, a cell wall component of Enterococcus faecalis (LT-2), stimulated a subpopulation of quiescent cells with high proliferative potential to divide (Elgavish et al., 1996b, J Cell Physiol 169:42-51). Studies were consistent with the possibility that NO-mediated mechanisms were involved (Elgavish et al., 1996c, J Cell Physiol 169:66-77). We postulated that LT-2 may upregulate expression of iNOS. Promoters of the gene encoding iNOS, as well as genes encoding many cytokines, contain elements homologous to consensus sequences for the binding of the transcription factor NF-kappaB. Based on this, we postulated that: (1) NF-kappaB activation is an early event following exposure of basal UT to LT-2 and (2) NF-kappaB activation mediates basal UT proliferation triggered by LT-2. To test these hypotheses, UT maintained for 3 days under growth-restricting conditions, were treated with or without 25 microg/ml LT-2. Nuclear distribution of NF-kappaB, that is, activated NF-kappaB, was detected by immunofluorescence microscopy in a subpopulation of basal UT as early as 5-10 min after the beginning of the treatment. In contrast, LT-2 had no effect on cultures containing more differentiated UT. NF-kappaB activation preceded production of NO, since treatment with 25 microM hemoglobin, a potent inactivator of NO, did not prevent LT-2-triggered NF-kappaB activation. Treatment with 10 microM pyrrolidine dithiocarbamate (PDTC) inhibited LT-2-triggered activation of NF-kappaB and prevented the stimulatory effect of LT-2 on proliferation of basal UT. These findings support the possibility that NF-kappaB activation mediates basal UT proliferation triggered by LT-2.
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    Keywords

  • Cell Wall, Cells, Cultured, Enterococcus faecalis, Enzyme Induction, Epithelial Cells, Humans, Lipopolysaccharides, NF-kappa B, Nitric Oxide Synthase, Pyrrolidines, Teichoic Acids, Thiocarbamates, Transcriptional Activation, Ureter
  • Author List

  • Elgavish A
  • Start Page

  • 232
  • End Page

  • 238
  • Volume

  • 182
  • Issue

  • 2