title: Modulation of calprotectin in human keratinocytes by keratinocyte growth factor and interleukin-1alpha.
abstract: Calprotectin is an antimicrobial complex composed of the S100A8 and S100A9 protein family subunits. Contributing to innate immunity, calprotectin expression is increased by interleukin-1alpha (IL-1alpha), which modulates keratinocyte differentiation. Keratinocyte growth factor (KGF) is produced by mesenchymal cells and has a mitogenic activity for epithelial cells. In this study, we investigated the effect of KGF on calprotectin expression in keratinocytes and modulation by IL-1alpha. Human keratinocytes were cultured with KGF in the presence or absence of a KGF receptor (KGFR) inhibitor or mitogen-activated protein kinase (MAPK) inhibitors. Calprotectin (S100A8/S100A9) expression was determined by northern blotting and enzyme-linked immunosorbent assay, respectively, whereas MAPK phosphorylation was analyzed by western blot analysis. KGF significantly decreased the expression of S100A8/S100A9-specific mRNAs and calprotectin protein. In the presence of KGF, KGFR inhibitor or extracellular-regulated kinase inhibitor restored KGF-downregulated expression of S100A8/S100A9. KGF increased IL-1alpha expression in keratinocytes, whereas IL-1alpha increased KGF expression in fibroblasts. Cocultured fibroblast and keratinocytes showed lower S100A8/S100A9 mRNA expression than keratinocytes alone in the presence or absence of IL-1alpha or KGF. These results suggest that fibroblast-derived KGF reduces or restricts calprotectin expression in keratinocytes, which supports our hypothesis that calprotectin expression in keratinocytes is modulated by factors associated with epithelial-mesenchymal interactions.
authors.affiliation: Department of Periodontology and Endodontology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Bando
authors.forename: Yuka
authors.initials: Y
authors.lastname: Hiroshima
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kataoka
authors.forename: Mark C
authors.initials: MC
authors.lastname: Herzberg
authors.forename: Karen F
authors.initials: KF
authors.lastname: Ross
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Shinohara
authors.forename: Takenori
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Nagata
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kido
mesh_terms: D040501:Calgranulin A / Q000096:biosynthesis*; D040502:Calgranulin B / Q000096:biosynthesis*; D002460:Cell Line; D018920:Coculture Techniques; D051523:Fibroblast Growth Factor 7 / Q000378:metabolism* / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism* / Q000494:pharmacology; D015603:Keratinocytes / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D053582:Interleukin-1alpha; D051523:Fibroblast Growth Factor 7; D020929:Mitogen-Activated Protein Kinase Kinases