S100A8/A9, a key mediator for positive feedback growth stimulation of normal human keratinocytes

Takamasa Nukui, Ritsuko Ehama, Masakiyo Sakaguchi, Hiroyuki Sonegawa, Chika Katagiri, Toshihiko Hibino, Nam Ho Huh

Research output: Contribution to journalArticlepeer-review

91 Citations (Scopus)


S100A8 and S100A9 are known to be up-regulated in hyperproliferative and psoriatic epidermis, but their function in epidermal keratinocytes remains largely unknown. Here we show that (1) S100A8 and S100A9 are secreted by cultured normal human keratinocytes (NHK) in a cytokine-dependent manner, (2) when applied to NHK, recombinant S100A8/A9 (a 1:1 mixture of S100A8 and S100A9) induced expression of a number of cytokine genes such as IL-8/CXCL8, CXCL1, CXCL2, CXCL3, CCL20, IL-6, and TNFα that are known to be up-regulated in psoriatic epidermis, (3) the S100A8/ A9-induced cytokines in turn enhanced production and secretion of S100A8 and S100A9 by NHK, and (4) S100A8 and S100A8/A9 stimulated the growth of NHK at a concentration as low as 1 ng/ml. These results indicate the presence of a positive feedback loop for growth stimulation involving S100A8/A9 and cytokines in human epidermal keratinocytes, implicating the relevance of the positive feedback loop to the etiology of hyperproliferative skin diseases, including psoriasis.

Original languageEnglish
Pages (from-to)453-464
Number of pages12
JournalJournal of Cellular Biochemistry
Issue number2
Publication statusPublished - May 15 2008


  • Inflammation
  • MRP
  • Psoriasis
  • S100

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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