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Transcription Factors Regulating Inflammatory Cytokine Production Are Differentially Expressed in Peripheral Blood Mononuclear Cells of Beh ç et Disease Depending on Disease Activity

View Article: PubMed Central - PubMed

ABSTRACT

Background: Behçet disease (BD) is a relapsing inflammatory disease with increased production of inflammatory cytokines in peripheral blood mononuclear cells (PBMCs); however, the underlying molecular mechanisms are not well known.

Objective: To analyze whether the differential expression of transcription factors is involved in the increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production by PBMCs of BD patients compared to healthy controls (HCs).

Methods: Expression of transcription factors was examined by real-time reverse transcriptase-polymerase chain reaction and western blotting. Cytokine production by CD11b+ cells transfected with siRNAs against transcription factors was measured by enzyme-linked immunosorbent assay.

Results: In the absence of lipopolysaccharide stimulation, the transcript level of CCAAT-enhancer-binding proteins (C/EBP) β was increased in PBMCs from patients with active BD compared to that in PBMCs from patients with stable BD. The C/EBPδ transcript level was higher in PBMCs from patients with active BD than in those from HCs. The activating transcription factor 3 (ATF3) transcript level was increased in PBMCs from patients with stable BD compared to that in PBMCs from HCs. siRNAs targeting C/EBPβ and C/EBPδ significantly reduced the production of IL-6 and TNF-α in lipopolysaccharide-stimulated CD11b+ cells from patients with BD as well as from HCs.

Conclusion: We found differential expression of C/EBPβ, C/EBPδ, and ATF3 in PBMCs from patients with BD depending on disease activity, indicating the involvement of these molecules in BD pathogenesis.

No MeSH data available.


Related in: MedlinePlus

Graphical summary. LPS: lipopolysccharide, ATF3: activating transcription factor 3, C/EBPβ LAP: CCAAT-enhancerbinding proteins β liver-enriched transcriptional-activator protein, HC: healthy controls, BD: Behcet disease, IL-6: interleukin-6, TNF-α: tumor necrosis factor-α.
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Figure 5: Graphical summary. LPS: lipopolysccharide, ATF3: activating transcription factor 3, C/EBPβ LAP: CCAAT-enhancerbinding proteins β liver-enriched transcriptional-activator protein, HC: healthy controls, BD: Behcet disease, IL-6: interleukin-6, TNF-α: tumor necrosis factor-α.

Mentions: In this study, we evaluated the involvement of transcription factors in the differential production of TNF-α and IL-6 in patients with BD. We showed differential expression of C/EBPβ, C/EBPδ, and ATF3; mRNA of C/EBPβ and C/EBPδ but not ATF3 was higher in PBMCs of active BD, whereas ATF3 mRNA was upregulated in PBMCs of stable BD. Further, a critical role for C/EBPβ and C/EBPδ in the production of TNF-α and IL-6 in CD11b+ cells of BD was demonstrated (Fig. 5).


Transcription Factors Regulating Inflammatory Cytokine Production Are Differentially Expressed in Peripheral Blood Mononuclear Cells of Beh ç et Disease Depending on Disease Activity
Graphical summary. LPS: lipopolysccharide, ATF3: activating transcription factor 3, C/EBPβ LAP: CCAAT-enhancerbinding proteins β liver-enriched transcriptional-activator protein, HC: healthy controls, BD: Behcet disease, IL-6: interleukin-6, TNF-α: tumor necrosis factor-α.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5383742&req=5

Figure 5: Graphical summary. LPS: lipopolysccharide, ATF3: activating transcription factor 3, C/EBPβ LAP: CCAAT-enhancerbinding proteins β liver-enriched transcriptional-activator protein, HC: healthy controls, BD: Behcet disease, IL-6: interleukin-6, TNF-α: tumor necrosis factor-α.
Mentions: In this study, we evaluated the involvement of transcription factors in the differential production of TNF-α and IL-6 in patients with BD. We showed differential expression of C/EBPβ, C/EBPδ, and ATF3; mRNA of C/EBPβ and C/EBPδ but not ATF3 was higher in PBMCs of active BD, whereas ATF3 mRNA was upregulated in PBMCs of stable BD. Further, a critical role for C/EBPβ and C/EBPδ in the production of TNF-α and IL-6 in CD11b+ cells of BD was demonstrated (Fig. 5).

View Article: PubMed Central - PubMed

ABSTRACT

Background: Behçet disease (BD) is a relapsing inflammatory disease with increased production of inflammatory cytokines in peripheral blood mononuclear cells (PBMCs); however, the underlying molecular mechanisms are not well known.

Objective: To analyze whether the differential expression of transcription factors is involved in the increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production by PBMCs of BD patients compared to healthy controls (HCs).

Methods: Expression of transcription factors was examined by real-time reverse transcriptase-polymerase chain reaction and western blotting. Cytokine production by CD11b+ cells transfected with siRNAs against transcription factors was measured by enzyme-linked immunosorbent assay.

Results: In the absence of lipopolysaccharide stimulation, the transcript level of CCAAT-enhancer-binding proteins (C/EBP) β was increased in PBMCs from patients with active BD compared to that in PBMCs from patients with stable BD. The C/EBPδ transcript level was higher in PBMCs from patients with active BD than in those from HCs. The activating transcription factor 3 (ATF3) transcript level was increased in PBMCs from patients with stable BD compared to that in PBMCs from HCs. siRNAs targeting C/EBPβ and C/EBPδ significantly reduced the production of IL-6 and TNF-α in lipopolysaccharide-stimulated CD11b+ cells from patients with BD as well as from HCs.

Conclusion: We found differential expression of C/EBPβ, C/EBPδ, and ATF3 in PBMCs from patients with BD depending on disease activity, indicating the involvement of these molecules in BD pathogenesis.

No MeSH data available.


Related in: MedlinePlus