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

• Published in: Annals of dermatology Vol. 29; no. 2; pp. 173 - 179
• Main Authors: Woo, Min-Yeong, Yun, Su Jin, Lee, Mi Jin, Kim, Kyongmin, Lee, Eun-So, Park, Sun
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Dermatological Association; The Korean Society for Investigative Dermatology 01.04.2017; 대한피부과학회
• Subjects: Original; 피부과학; Behcet syndrome; Tumor necrosis factor-alpha; CCAAT-enhancer-binding proteins; Gene expression; Interleukin-6
• ISSN: 1013-9087; 2005-3894
• DOI: 10.5021/ad.2017.29.2.173

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. 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). 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. 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. 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.