title: Keratinocyte-specific modulation of type VII collagen gene expression by pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1beta).
abstract: 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.
authors.affiliation: Department of Dermatology, Hirosaki University School of Medicine, Hirosaki, Aomori, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takeda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kon
authors.forename: Noriko
authors.initials: N
authors.lastname: Ito
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sawamura
authors.forename: Keiichi
authors.initials: K
authors.lastname: Takagaki
authors.forename: Isao
authors.initials: I
authors.lastname: Hashimoto
authors.forename: Katsumi
authors.initials: K
authors.lastname: Hanada
mesh_terms: 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
chemical_list: D024143:Collagen Type VII; D016207:Cytokines; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha