کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1946468 1054241 2013 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mechanism of interleukin-1α transcriptional regulation of S100A9 in a human epidermal keratinocyte cell line
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Mechanism of interleukin-1α transcriptional regulation of S100A9 in a human epidermal keratinocyte cell line
چکیده انگلیسی


• S100A9 expression in epidermal keratinocytes is upregulated by IL-1α.
• IL-1α signals S100A9 expression via IL-1R1, p38 and C/EBPβ.
• Blocking IL-1R or suppression of p38 MAPK reduced IL-1α-induced S100A9 expression.
• IL-1α induced C/EBPβ binding activity, which was required for S100A9 expression.

S100A9 is a calcium-binding protein and subunit of antimicrobial calprotectin complex (S100A8/A9). Produced by neutrophils, monocytes/macrophages and keratinocytes, S100A9 expression increases in response to inflammation. For example, IL-1α produced by epithelial cells acts autonomously on the same cells to induce the expression of S100A8/A9 and cellular differentiation. Whereas it is well known that IL-1α and members of the IL-10 family of cytokines upregulate S100A8 and S100A9 in several cell lineages, the pathway and mechanism of IL-1α-dependent transcriptional control of S100A9 in epithelial cells are not established. Modeled using human epidermal keratinocytes (HaCaT cells), IL-1α stimulated the phosphorylation of p38 MAPK and induced S100A9 expression, which was blocked by IL-1 receptor antagonist, RNAi suppression of p38, or a p38 MAPK inhibitor. Transcription of S100A9 in HaCaT cells depended on nucleotides − 94 to − 53 in the upstream promoter region, based upon the use of deletion constructs and luciferase reporter activity. Within the responsive promoter region, IL-1α increased the binding activity of CCAAT/enhancer binding protein β (C/EBPβ). Mutated C/EBPβ binding sequences or C/EBPβ-specific siRNA inhibited the S100A9 transcriptional response. Hence, IL-1α is strongly suggested to increase S100A9 expression in a human epidermal keratinocyte cell line by signaling through the IL-1 receptor and p38 MAPK, increasing C/EBPβ-dependent transcriptional activity.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms - Volume 1829, Issue 9, September 2013, Pages 954–962
نویسندگان
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