カルプロテクチンの培養上皮細胞における発現調節

  • 廣島 佑香
    徳島大学大学院ヘルスバイオサイエンス研究部歯周歯内治療学分野
  • 板東 美香
    徳島大学大学院ヘルスバイオサイエンス研究部歯周歯内治療学分野
  • 片岡 正俊
    産業技術総合研究所健康工学研究センター
  • 永田 俊彦
    徳島大学大学院ヘルスバイオサイエンス研究部歯周歯内治療学分野
  • 木戸 淳一
    徳島大学大学院ヘルスバイオサイエンス研究部歯周歯内治療学分野

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  • Regulation of calprotectin expression in human keratinocytes in vitro

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Calprotectin, a heterodimeric complex of S100A8 and S100A9, is an antimicrobial peptide (AMP) expressed in healthy or inflamed epithelium and epidermis. The expression of calprotectin and other AMPs in keratinocytes is regulated by proinflammatory cytokines, bacterial products and keratinocyte differentiation modulators. Interleukin-1α (IL-1α), an autonomous cytokine in keratinocytes, induces keratinocyte differentiation and up-regulates calprotectin expression. Since keratinocyte differentiation is also specified<KG>by interactions with the basement membrane and connective tissue proteins, we sought to learn whether calprotectin expression is affected by extracellular matrix (ECM) proteins in the presence or absence of IL-1α. Human immortalized epidermal keratinocytes (HaCaT cells) were grown in vitro on different ECM substrates including type I collagen (Col I), type IV collagen (Col IV), fibronectin (FN) and laminin (LM) with or without IL-1α and were then cultured in basement membrane extract (Matrigel)-coated dishes or on a feeder layer of fibroblasts. Calprotectin expression in the cultured cells was investigated using immunohistochemical and northern blot analyses, and an enzyme-linked immunosorbent assay. The four ECM proteins (Col I, Col IV, FN and LM) had little effect on calprotectin expression. IL-1α significantly increased the expression of S100A8/ S100A9 mRNAs and calprotecin protein in the cells cultured on each of the ECM(Col I, Col IV, FN and LM)-coated dishes,but these ECM protein substrates did not show a further effect on calprotectin expression in the presence of IL-1α. On the other hand, Matrigel and the fibroblast-feeder layer slightly decreased the expression of S100A8/S100A9 mRNAs in HaCaT cells. These results suggest that calprotectin expression in keratinocytes is regulated by cytokines during epithelial-mesenchymal interactions.<KG>Nihon Shishubyo Gakkai Kaishi (J Jpn Periodontol) 49 : 224-232,2007.

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