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  • Title: Keratinocyte-specific modulation of type VII collagen gene expression by pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1beta).
    Author: Takeda H, Kon A, Ito N, Sawamura D, Takagaki K, Hashimoto I, Hanada K.
    Journal: Exp Dermatol; 2005 Apr; 14(4):289-94. PubMed ID: 15810887.
    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.
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