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Molecular and Cellular Biology, March 1999, p. 1950-1960, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Reactive Oxygen Intermediate-Dependent NF-kappa B Activation by Interleukin-1beta Requires 5-Lipoxygenase or NADPH Oxidase Activity

Giuseppina Bonizzi,1 Jacques Piette,2 Sonia Schoonbroodt,2 Roland Greimers,3 Laurence Havard,1 Marie-Paule Merville,1 and Vincent Bours1,*

Laboratory of Medical Chemistry/Medical Oncology,1 Laboratory of Fundamental Virology,2 and Laboratory of Pathology,3 University of Liège, Liège, Belgium

Received 16 July 1998/Returned for modification 26 August 1998/Accepted 30 November 1998

We previously reported that the role of reactive oxygen intermediates (ROIs) in NF-kappa B 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-1beta (IL-1beta ) led to ROI production and NF-kappa B 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-kappa B activation in these cells. IL-1beta stimulation of epithelial cells did not generate any ROIs and NF-kappa B 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-kappa B activation. In monocytic cells, IL-1beta 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-kappa B activation by IL-1beta in epithelial cells. In conclusion, three different cell-specific pathways lead to NF-kappa B activation by IL-1beta : 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.

* Corresponding author. Mailing address: Medical Oncology, CHU B35, Sart-Tilman, Université de Liège, 4000 Liège, Belgium. Phone: 32-4-3662482. Fax: 32-4-3664534. E-mail: vbours{at}ulg.ac.be.

Molecular and Cellular Biology, March 1999, p. 1950-1960, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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