Mast cell activation triggers a urothelial inflammatory response mediated by tumor necrosis factor-α

Robert A. Batler, Shomit Sengupta, Sarah G. Forrestal, Anthony J. Schaeffer*, David J. Klumpp

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Purpose: Mast cells have been implicated in bladder inflammation and pathogenesis. To determine if mast cell secretion products can modulate urothelial inflammatory responses we developed an in vitro model of mast cell-urothelial cell interactions. Materials and Methods: Cultures of the immortalized urothelial cell line TEU-2 were incubated in the conditioned medium of mast cell cultures. The urothelial inflammatory response to mast cell secretion products was then determined by quantifying nuclear factor κB activity, the expression of endogenous nuclear factor κB dependent genes and the protein expression of inflammation markers. Results: Conditioned medium from RBL-2H3 mast cells induced a 4-fold increase in TEU-2 nuclear factor κB activity that was independent of the activation state of the mast cells. In contrast, ribonuclease protection assays revealed that the nuclear factor κB dependent transcripts tumor necrosis factor-α (TNF-α), interleukin (IL) 8 and 1β, and intracellular adhesion molecule 1 (ICAM-1) were induced by mast cell conditioned medium in a manner that strictly depended on mast cell activation (antigen challenge of IgE sensitized RBL-2H3 cells). The dependence on mast cell activation was confirmed by the observation that IL-8 secretion and ICAM-1 protein expression in TEU-2 cultures were induced only by conditioned medium of stimulated RBL-2H3 cells The induction of TEU-2 IL-8 secretion and ICAM-1 expression by mast cell conditioned medium could be blocked by an anti-TNF-α antibody or the cysteine protease inhibitor N-acetyl-leucinyl-leucinyl-norleucinal. Conclusions: Our data support the hypothesis that mast cells may participate in bladder inflammation. Furthermore, TNF-α acting via the nuclear factor κB signaling pathway may be a mediator of the urothelial response to mast cell secretion products.

Original languageEnglish (US)
Pages (from-to)819-825
Number of pages7
JournalJournal of Urology
Issue number2
StatePublished - 2002


  • Bladder
  • Inflammation
  • Mast cells
  • Tumor necrosis factor
  • Urothelium

ASJC Scopus subject areas

  • Urology


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