An NF-kappaB-dependent role for JunB in the induction of proinflammatory cytokines in LPS-activated bone marrow-derived dendritic cells.
BACKGROUND
Dendritic cells (DCs) play a key role in the induction of adaptive and memory immune responses. Upon encounter with pathogens, they undergo a complex maturation process and migrate toward lymphoid organs where they stimulate immune effector cells. This process is associated with dramatic transcriptome changes, pointing to a paramount role for transcription factors in DC activation and function. The regulation and the role of these transcription factors are however ill-defined and require characterization. Among those, AP-1 is a family of dimeric transcription complexes with an acknowledged role in the control of immunity. However, it has not been studied in detail in DCs yet.


RESULTS
Here, we have investigated the regulation and function of one of its essential components, JunB, in primary bone marrow-derived DCs induced to maturate upon stimulation by Escherichia coli lipopolysaccharide (LPS). Our data show fast and transient NF-kappaB-dependent transcriptional induction of the junb gene correlating with the induction of the TNFalpha, IL-6, and IL-12 proinflammatory cytokines. Inhibition of JunB protein induction by RNA interference hampered the transcriptional activation of the TNF-alpha, IL-6, and IL-12p40 genes. Consistently, chromatin immunoprecipitation experiments showed LPS-inducible binding of JunB at AP-1-responsive sites found in promoter regions of these genes. Concomitant LPS-inducible NF-kappaB/p65 binding to these promoters was also observed.


CONCLUSIONS
We identified a novel role for JunB--that is, induction of proinflammatory cytokines in LPS-activated primary DCs with NF-kappaB acting not only as an inducer of JunB, but also as its transcriptional partner.
Gomard
Tiphanie
T
Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique, Montpellier, France.
Michaud
Henri-Alexandre
HA
Tempé
Denis
D
Thiolon
Kevin
K
Pelegrin
Mireia
M
Piechaczyk
Marc
M
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002843:Chromatin / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D004926:Escherichia coli / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D019084:Fluorescent Antibody Technique, Indirect; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation; D008070:Lipopolysaccharides / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation
D002843:Chromatin; D008070:Lipopolysaccharides; D016328:NF-kappa B; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; D051550:I-kappa B Kinase