Distinct Signal Transduction Pathways Mediate Nuclear Factor-κB Induction by IL-1β in Epithelial and Lymphoid Cells

Giuseppina Bonizzi, Jacques Piette, Marie Paule Merville, Vincent Bours

Research output: Contribution to journalArticle

Abstract

We previously demonstrated that IL-1β-mediated induction of the nuclear factor-κB (NF-κB) transcription factor proceeds through the production of reactive oxygen intermediates in lymphoid cells, while it occurs independently of any oxidative stress in epithelial transformed cells. Indeed, inhibition of receptor internalization as well as NH4Cl and chloroquine blocked IL-1β-mediated induction of NF-κB in OVCAR-3 and in other epithelial cell lines but not in lymphoid cells, indicating that distinct pathways are involved. Conversely, while we observed phospholipase A2 activity in both cell types following IL-1βstimulation, specific inhibitors of this enzyme inhibited NF-κB induction only in lymphoid cells. Moreover, expression of the 5-lipoxygenase (5-LOX) enzyme was not detected in epithelial cells, and inhibition of this enzyme blocked NF-κB induction by IL-1β only in lymphoid cells. This study thus indicates that the activation of NF-κB following IL-1β treatment involves the activation of phospholipase A2 and 5-LOX and the production of reactive oxygen intermediates (ROIs) in lymphoid cells, while in epithelial cells, another pathway predominates and could involve the acid sphingomyelinase. Moreover, arachidonic acid could induce NF-κB in epithelial and lymphoid cells, but this activation involved the 5-LOX enzyme and the production of ROIs only in lymphoid cells. The inefficiency of the ROI pathway in epithelial cells is probably the consequence of both low ROI production due to undetectable expression of 5-LOX and rapid degradation of hydrogen peroxide due to high catalase activity.

Original languageEnglish
Pages (from-to)5264-5272
Number of pages9
JournalJournal of Immunology
Volume159
Issue number11
Publication statusPublished - Dec 1 1997

ASJC Scopus subject areas

  • Immunology

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