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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2833204?pdf=render |
| _version_ | 1811227215811051520 |
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| author | Tiphanie Gomard Henri-Alexandre Michaud Denis Tempé Kevin Thiolon Mireia Pelegrin Marc Piechaczyk |
| author_facet | Tiphanie Gomard Henri-Alexandre Michaud Denis Tempé Kevin Thiolon Mireia Pelegrin Marc Piechaczyk |
| author_sort | Tiphanie Gomard |
| collection | DOAJ |
| description | 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-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/SIGNIFICANCE: 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. |
| first_indexed | 2024-04-12T09:37:51Z |
| format | Article |
| id | doaj.art-5e2eb5ed204840aeb9341ccebf3d1619 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T09:37:51Z |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5e2eb5ed204840aeb9341ccebf3d16192022-12-22T03:38:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0153e958510.1371/journal.pone.0009585An NF-kappaB-dependent role for JunB in the induction of proinflammatory cytokines in LPS-activated bone marrow-derived dendritic cells.Tiphanie GomardHenri-Alexandre MichaudDenis TempéKevin ThiolonMireia PelegrinMarc PiechaczykBACKGROUND: 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-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/SIGNIFICANCE: 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.http://europepmc.org/articles/PMC2833204?pdf=render |
| spellingShingle | Tiphanie Gomard Henri-Alexandre Michaud Denis Tempé Kevin Thiolon Mireia Pelegrin Marc Piechaczyk An NF-kappaB-dependent role for JunB in the induction of proinflammatory cytokines in LPS-activated bone marrow-derived dendritic cells. PLoS ONE |
| title | An NF-kappaB-dependent role for JunB in the induction of proinflammatory cytokines in LPS-activated bone marrow-derived dendritic cells. |
| title_full | An NF-kappaB-dependent role for JunB in the induction of proinflammatory cytokines in LPS-activated bone marrow-derived dendritic cells. |
| title_fullStr | An NF-kappaB-dependent role for JunB in the induction of proinflammatory cytokines in LPS-activated bone marrow-derived dendritic cells. |
| title_full_unstemmed | An NF-kappaB-dependent role for JunB in the induction of proinflammatory cytokines in LPS-activated bone marrow-derived dendritic cells. |
| title_short | An NF-kappaB-dependent role for JunB in the induction of proinflammatory cytokines in LPS-activated bone marrow-derived dendritic cells. |
| title_sort | nf kappab dependent role for junb in the induction of proinflammatory cytokines in lps activated bone marrow derived dendritic cells |
| url | http://europepmc.org/articles/PMC2833204?pdf=render |
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