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

ABSTRACT: 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-1? 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-1? and members of the IL-10 family of cytokines upregulate S100A8 and S100A9 in several cell lineages, the pathway and mechanism of IL-1?-dependent transcriptional control of S100A9 in epithelial cells are not established. Modeled using human epidermal keratinocytes (HaCaT cells), IL-1? 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-1? increased the binding activity of CCAAT/enhancer binding protein ? (C/EBP?). Mutated C/EBP? binding sequences or C/EBP?-specific siRNA inhibited the S100A9 transcriptional response. Hence, IL-1? 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/EBP?-dependent transcriptional activity.

SUBMITTER: Bando M 

PROVIDER: S-EPMC3719387 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature