An NF-κB-dependent role for JunB in the induction of proinflammatory cytokines in LPS-activated bone marrow-derived dendritic cells

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Abstract

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. Methodology/Principal Findings: 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-κB-dependent transcriptional induction of the junb gene correlating with the induction of the TNFα, IL-6, and IL-12 proinflammatory cytokines. Inhibition of JunB protein induction by RNA interference hampered the transcriptional activation of the TNF-α, 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-κB/p65 binding to these promoters was also observed. Conclusions/Significance: We identified a novel role for JunB-that is, induction of proinflammatory cytokines in LPS-activated primary DCs with NF-κB acting not only as an inducer of JunB, but also as its transcriptional partner. © 2010 Gomard et al.

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APA

Gomard, T., Michaud, H. A., Tempé, D., Thiolon, K., Pelegrin, M., & Piechaczyk, M. (2010). An NF-κB-dependent role for JunB in the induction of proinflammatory cytokines in LPS-activated bone marrow-derived dendritic cells. PLoS ONE, 5(3). https://doi.org/10.1371/journal.pone.0009585

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