NF-kappaB activation in response to toxical and therapeutical agents: role in inflammation and cancer treatment.
The NF-kappaB transcription factor is ubiquitously expressed and controls the expression of a large number of genes. Experimental data clearly indicate that NF-kappaB is a major regulator of the inflammatory reaction by controlling the expression of pro-inflammatory molecules in response to cytokines, oxidative stress and infectious agents. We demonstrated that NF-kappaB activation by IL-1beta follows three distinct cell-specific pathways. Moreover, our studies indicated that in one model of inflammatory diseases, horse recurrent airway obstruction (RAO), the extent of NF-kappaB basal activity correlates with pulmonary dysfunction. Another role of NF-kappaB activity protects cancer cells against apoptosis and could participate in the resistance to cancer treatment. However, we did not observe any increased cytotoxicity after treatment with anticancer drugs or TNF-alpha of cells expressing a NF-kappaB inhibitor. Therefore, we can conclude that the inhibition of apoptosis by NF-kappaB is likely to be cell type and stimulus-dependent. Further studies are required to determine whether NF-kappaB could be a target for anticancer treatments.
Bours
V
V
Laboratory of Medical Chemistry and Medical Oncology, Faculty of Medicine, University of Liège, CHU Tour de Pathologie B35, 4000 Sart-Tilman par, 1, Liège, Belgium. vbours@ulg.ac.be
Bonizzi
G
G
Bentires-Alj
M
M
Bureau
F
F
Piette
J
J
Lekeux
P
P
Merville
M
M
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000473:pathology* / Q000517:prevention & control; D016328:NF-kappa B / Q000187:drug effects / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000517:prevention & control
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D016328:NF-kappa B