Mechanism of interleukin-1α transcriptional regulation of S100A9 in a human epidermal keratinocyte cell line

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