Reactive oxygen intermediate-dependent NF-κB activation by interleukin- 1β requires 5-lipoxygenase or NADPH oxidase activity

Giuseppina Bonizzi, Jacques Piette, Sonia Schoonbroodt, Roland Greimers, Laurence Havard, Marie Paule Merville, Vincent Bours

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Abstract

We previously reported that the role of reactive oxygen intermediates (ROIs) in NF-κB activation by proinflammatory cytokines was cell specific. However, the sources for ROIs in various cell types are yet to be determined and might include 5-lipoxygenase (5-LOX) and NADPH oxidase. 5-LOX and 5-LOX activating protein (FLAP) are coexpressed in lymphoid cells but not in monocytic or epithelial cells. Stimulation of lymphoid cells with interleukin-1β (IL-1β) led to ROI production and NF-κB activation, which could both be blocked by antioxidants or FLAP inhibitors, confirming that 5- LOX was the source of ROIs and was required for NF-κB activation in these cells. IL-1β stimulation of epithelial cells did not generate any ROIs and NF-κB induction was not influenced by 5-LOX inhibitors. However, reintroduction of a functional 5-LOX system in these cells allowed ROI production and 5-LOX-dependent NF-κB activation. In monocytic cells, IL-1β treatment led to a production of ROIs which is independent of the 5-LOX enzyme but requires the NADPH oxidase activity. This pathway involves the Rac1 and Cdc42 GTPases, two enzymes which are not required for NF-κB activation by IL-1β in epithelial cells. In conclusion, three different cell-specific pathways lead to NF-κB activation by IL-1β: a pathway dependent on ROI production by 5-LOX in lymphoid cells, an ROI- and 5-LOX- independent pathway in epithelial cells, and a pathway requiring ROI production by NADPH oxidase in monocytic cells.

Original languageEnglish
Pages (from-to)1950-1960
Number of pages11
JournalMolecular and Cellular Biology
Volume19
Issue number3
Publication statusPublished - Mar 1999

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Bonizzi, G., Piette, J., Schoonbroodt, S., Greimers, R., Havard, L., Merville, M. P., & Bours, V. (1999). Reactive oxygen intermediate-dependent NF-κB activation by interleukin- 1β requires 5-lipoxygenase or NADPH oxidase activity. Molecular and Cellular Biology, 19(3), 1950-1960.