title: Mechanism of interleukin-1α 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-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.
authors.affiliation: Department of Periodontology and Endodontology, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Bando
authors.forename: Xianqiong
authors.initials: X
authors.lastname: Zou
authors.forename: Yuka
authors.initials: Y
authors.lastname: Hiroshima
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kataoka
authors.forename: Karen F
authors.initials: KF
authors.lastname: Ross
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Shinohara
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Nagata
authors.forename: Mark C
authors.initials: MC
authors.lastname: Herzberg
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kido
mesh_terms: D001483:Base Sequence; D040502:Calgranulin B / Q000235:genetics*; D002460:Cell Line; D017931:DNA Primers; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D053582:Interleukin-1alpha / Q000502:physiology*; D015603:Keratinocytes / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D014158:Transcription, Genetic / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D040502:Calgranulin B; D017931:DNA Primers; D053582:Interleukin-1alpha; D048051:p38 Mitogen-Activated Protein Kinases
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
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