Keratinocyte-specific modulation of type VII collagen gene expression by pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1beta).
Previous studies have shown that pro-inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta up-regulate type VII collagen gene (COL7A1) expression in cultured dermal fibroblasts. The present study was designed to investigate the effects of TNF-alpha and IL-1beta on COL7A1 expression in epidermal keratinocytes. We demonstrated that both TNF-alpha and IL-1beta reduced COL7A1 expression in epidermal keratinocytes in an additive manner, whereas they increased COL7A1 expression in dermal fibroblasts. Thus, regulation of COL7A1 by pro-inflammatory cytokines is cell type specific. In particular, the inhibitory effects of TNF-alpha and IL-1beta occurred, at least in part, at the transcriptional level. Finally, we demonstrated that TNF-alpha and IL-1beta enhanced the TGF-beta-mediated up-regulation of COL7A1 expression in HaCaT keratinocytes, suggesting that the combination of TGF-beta and TNF-alpha or IL-1beta induces a signaling pathway that is completely different from that induced by either pro-inflammatory cytokine alone.
Takeda
Hitoshi
H
Department of Dermatology, Hirosaki University School of Medicine, Hirosaki, Aomori, Japan.
Kon
Atsushi
A
Ito
Noriko
N
Sawamura
Daisuke
D
Takagaki
Keiichi
K
Hashimoto
Isao
I
Hanada
Katsumi
K
D015153:Blotting, Western; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D024143:Collagen Type VII / Q000737:chemistry*; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D007375:Interleukin-1 / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
D024143:Collagen Type VII; D016207:Cytokines; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha