BCP Symposium PresentationCell type-specific role for reactive oxygen species in nuclear factor-kappaB activation by Interleukin-1
Section snippets
Lymphoid cells
Stimulation of lymphoid cells (70Z/3, Raji, or EL-4 cell lines) with IL-1β generates ROIs and rapidly induces nuclear NF-κB DNA-binding activity. We could demonstrate that ROI production was required for IL-1β-induced NF-κB DNA binding, IκB-α degradation, and NF-κB-dependent transactivation, as these activities were blocked by the antioxidants NAC and PDTC. We then identified 5-LOX as the main source of ROIs in these cells after IL-1β treatment. Indeed, the above-mentioned lymphoid cells
Monocytic cells
Stimulation of monocytic cells (U937 and THP-1 cell lines) with IL-1β also generates ROIs and potently activates NF-κB. As in lymphoid cells, preincubation of these cells with the antioxidants NAC and PDTC inhibits both the production of ROIs and NF-κB nuclear activity, thus indicating that the pathway leading to IκB-α degradation requires ROI production. However, the source of ROIs was different than in lymphoid cells. Indeed, the monocytic cell lines we analyzed do not express the 5-LOX
Epithelial cells
In the various epithelial cell lines we explored (MCF7 A/Z, OVCAR-3, HCT116, and SKOV-3), IL-1β induced a strong NF-κB nuclear activity, but did not activate ROI production. Therefore, NF-κB activation and IκB-α degradation were not affected by antioxidants in these cells. There are two possible explanations for the lack of ROI production in these cells. Epithelial cells, such as OVCAR-3 cells, express high levels of catalase activity. Moreover, none of the epithelial cell lines we analyzed
Discussion
Although the role of ROIs in NF-κB activation by proinflammatory cytokines and other stimulating agents was reported several years ago, it has become very much a matter of controversy since the cloning of the IKKs. Several authors have recently described a direct pathway for NF-κB activation by IL-1β which links the receptor, receptor-associated adaptor proteins and kinases (MyD88, Il-1 receptor-associated kinase (IRAK), and TNF receptor-associated kinase factors 6 (TRAF6)), the NIK or MEKK-1
Acknowledgements
M-P.M. and V.B. are research associates and J.P. is a research director at the National Fund for Scientific Research (FNRS, Belgium). G.B. is a fellow from the Biotechnology Programme, European Commission.
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