S100A8/A9, a key mediator for positive feedback growth stimulation of normal human keratinocytes.
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 TNFalpha 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.
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikatachou, Okayama 700-8558, Japan.
Takamasa
T
Nukui
Ritsuko
R
Ehama
Masakiyo
M
Sakaguchi
Hiroyuki
H
Sonegawa
Chika
C
Katagiri
Toshihiko
T
Hibino
Nam-Ho
NH
Huh
D040501:Calgranulin A; D040502:Calgranulin B; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics; D025461:Feedback, Physiological; D006801:Humans; D015603:Keratinocytes / Q000166:cytology*; D011565:Psoriasis / Q000209:etiology; D009418:S100 Proteins / Q000502:physiology*; D015854:Up-Regulation
D040501:Calgranulin A; D040502:Calgranulin B; D016207:Cytokines; D009418:S100 Proteins