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- Title
Modulation of calprotectin in human keratinocytes by keratinocyte growth factor and interleukin-1α.
- Authors
Bando, Mika; Hiroshima, Yuka; Kataoka, Masatoshi; Herzberg, Mark C.; Ross, Karen F.; Shinohara, Yasuo; Yamamoto, Takenori; Nagata, Toshihiko; Kido, Jun-ichi
- 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-1α (IL-1α), 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-1α. 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-1α expression in keratinocytes, whereas IL-1α 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-1α 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.
- Subjects
ANTI-infective agents; NATURAL immunity; KERATINOCYTE differentiation; INTERLEUKIN-1; EPITHELIAL cells; GROWTH factors
- Publication
Immunology & Cell Biology, 2010, Vol 88, Issue 3, p328
- ISSN
0818-9641
- Publication type
Article
- DOI
10.1038/icb.2009.104