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S100A8/A9, a key mediator for positive feedback growth stimulation of normal human keratinocytes
Author(s) -
Nukui Takamasa,
Ehama Ritsuko,
Sakaguchi Masakiyo,
Sonegawa Hiroyuki,
Katagiri Chika,
Hibino Toshihiko,
Huh NamHo
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21639
Subject(s) - s100a9 , epidermis (zoology) , s100a8 , cxcl1 , cytokine , keratinocyte , stimulation , psoriasis , biology , cxcl2 , microbiology and biotechnology , chemokine , inflammation , immunology , cell culture , endocrinology , anatomy , genetics , chemokine receptor
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. J. Cell. Biochem. 104: 453–464, 2008. © 2007 Wiley‐Liss, Inc.