S100A8 and S100A9 are messengers in the crosstalk between epidermis and dermis modulating a psoriatic milieu in human skin.
S100A8 and S100A9 are members of the S100A8 protein family that exist as homodimers and heterodimers in neutrophils, monocytes, and macrophages. Recent studies have shown the pivotal roles of S100A8 and S100A9 in the propagation of inflammation and keratinocyte proliferation in psoriasis. We found significant up-regulation of S100A8 and S100A9 secretion from keratinocytes in psoriatic lesions. To mimic the in vivo secretory conditions of S100A8 and S100A9 from psoriatic epidermal keratinocytes, we used the culture medium (CM) of S100A8 and S100A8/A9 adenovirus-transduced keratinocytes to investigate the functions of S100A8 and S100A9. We detected increased levels of various pro-inflammatory cytokines in the CM, including IL-8 and TNF-α, which are involved in aggravating psoriatic skin lesions, and IL-6 and members of the CXCL family of pro-angiogenic cytokines. The CM increased immune cell migration and increased angiogenesis in human umbilical vein endothelial cells. In conclusion, we found that the upregulated production of S100A8 and S100A9 by psoriatic epidermal keratinocytes activated adjacent keratinocytes to produce several cytokines. Moreover, S100A8 and S100A9 themselves function as pro-angiogenic and chemotactic factors, generating a psoriatic milieu in skin.
Department of Dermatology, College of Medicine, Chungnam National University, Daejeon, South Korea.
Young
Y
Lee
Sunhyae
S
Jang
Jeong-Ki
JK
Min
Kyungmin
K
Lee
Kyung-Cheol
KC
Sohn
Jong-Soon
JS
Lim
Myung
M
Im
Hae-Eul
HE
Lee
Young-Joon
YJ
Seo
Chang-Deok
CD
Kim
Jeung-Hoon
JH
Lee
D040501:Calgranulin A / Q000235:genetics / Q000378:metabolism*; D040502:Calgranulin B / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D020405:Dermis / Q000276:immunology* / Q000473:pathology; D042783:Endothelial Cells / Q000473:pathology; D004817:Epidermis / Q000276:immunology* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D015603:Keratinocytes / Q000276:immunology*; D018919:Neovascularization, Physiologic; D055503:Protein Multimerization; D011565:Psoriasis / Q000276:immunology* / Q000473:pathology
D040501:Calgranulin A; D040502:Calgranulin B; D016207:Cytokines