Lipopolysaccharide from Salmonella enterica activates NF-kappaB through both classical and alternative pathways in primary B Lymphocytes.
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.
Souvannavong
Vongthip
V
CNRS, Institut de Biochimie Biophysique Moléculaire et Cellulaire, UMR 8619, Université Paris-Sud, Bat. 430, 91405 Orsay cedex, France. vongthip.souvannavong@u-psud.fr
Saidji
Nabila
N
Chaby
Richard
R
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002467:Cell Nucleus / Q000737:chemistry; D002478:Cells, Cultured; D003600:Cytosol / Q000737:chemistry; D019281:Dimerization; D005260:Female; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000032:analysis; D015151:Immunoblotting; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D052003:NF-kappa B p52 Subunit / Q000378:metabolism; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019779:Salmonella enterica / Q000276:immunology*; D051996:Transcription Factor RelA / Q000378:metabolism; D051841:Transcription Factor RelB / Q000378:metabolism
C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; C491366:Nfkbie protein, mouse; D011518:Proto-Oncogene Proteins; C498144:Rela protein, mouse; C497594:Relb protein, mouse; D051996:Transcription Factor RelA; C073701:Nfkb1 protein, mouse; D051841:Transcription Factor RelB; D051550:I-kappa B Kinase
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