[en] We previously reported that the role of reactive oxygen intermediates (ROIs) in NF-kappaB 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-kappaB 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-kappaB activation in these cells. IL-1beta stimulation of epithelial cells did not generate any ROIs and NF-kappaB 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-kappaB 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-kappaB activation by IL-1beta in epithelial cells. In conclusion, three different cell-specific pathways lead to NF-kappaB 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.
Disciplines :
Oncology
Author, co-author :
Bonizzi, Giuseppina
Piette, Jacques ; Université de Liège - ULiège > Département des sciences de la vie > Virologie - Immunologie
Haterte, Stéphanie ; Université de Liège - ULiège > Département des sciences de la santé publique > Informatique médicale et biostatistique
Greimers, Roland ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Havard, Laurence
Merville, Marie-Paule ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Bours, Vincent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique générale et humaine
Language :
English
Title :
Reactive Oxygen Intermediate-Dependent Nf-Kappab Activation by Interleukin-1beta Requires 5-Lipoxygenase or Nadph Oxidase Activity
Publication date :
March 1999
Journal title :
Molecular and Cellular Biology
ISSN :
0270-7306
eISSN :
1098-5549
Publisher :
American Society for Microbiology, Washington, United States - District of Columbia
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