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Biochim Biophys Acta. 2013 Sep;1829(9):954-62. doi: 10.1016/j.bbagrm.2013.03.010. Epub 2013 Apr 3.

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

Author information

1
Department of Periodontology and Endodontology, The University of Tokushima Graduate School, Tokushima, Japan.

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-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.

KEYWORDS:

C/EBPβ; ERK; IL-1 receptor; IL-1R1; IL-1α; JNK; Keratinocytes; S100A9; TLR5; Toll-like receptor 5; c-JUN N-terminal kinase; extracellular-regulated kinase; p38; p38 kinase; siRNA; small interfering RNA

PMID:
23563247
PMCID:
PMC3719387
DOI:
10.1016/j.bbagrm.2013.03.010
[Indexed for MEDLINE]
Free PMC Article
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