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  • Title: Lipopolysaccharide from Salmonella enterica activates NF-kappaB through both classical and alternative pathways in primary B Lymphocytes.
    Author: Souvannavong V, Saidji N, Chaby R.
    Journal: Infect Immun; 2007 Oct; 75(10):4998-5003. PubMed ID: 17698569.
    Abstract:
    Lipopolysaccharides (LPS) are potent polyclonal B-lymphocyte activators. Recently, we have shown that LPS inhibits both spontaneous and drug-induced apoptosis in mature B lymphocytes, through cytosolic retention of Bax, a proapoptotic protein of the Bcl-2 family, by preventing its translocation to mitochondria. Research within the last few years has revealed that members of the NF-kappaB transcription factor regulate cell viability by activating genes involved in mitochondrion-dependent apoptosis. In this report, we examined the effect of sustained LPS stimulation on cytosolic and nuclear proteins of the IkappaB/NF-kappaB family to determine which NF-kappaB pathway, canonical (classical) or noncanonical (alternative), is activated by this agent in mature B cells. Immunoblotting analyses showed that LPS induced a time-dependent degradation of the NF-kappaB inhibitors IkappaBbeta and IkappaBepsilon (preferentially to isoform IkappaBalpha), via IkappaB kinase beta. In addition, we observed that LPS triggered the processing of NF-kappaB p105 to p50 and that of NF-kappaB p100 to p52 in parallel with nuclear translocation of active p50 and p52, as NF-kappaBp50/RelA and NF-kappaBp52/RelB heterodimers, respectively. These results suggest that sustained stimulation with LPS can activate NF-kappaB through both classical and alternative pathways.
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