Keratinocyte‐specific modulation of type VII collagen gene expression by pro‐inflammatory cytokines (tumor necrosis factor‐α and interleukin‐1β)

:  Previous studies have shown that pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β up-regulate type VII collagen gene (COL7A1) expression in cultured dermal fibroblasts. The present study was designed to investigate the effects of TNF-α and IL-1β on COL7A1 expression in epidermal keratinocytes. We demonstrated that both TNF-α and IL-1β 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-α and IL-1β occurred, at least in part, at the transcriptional level. Finally, we demonstrated that TNF-α and IL-1β enhanced the TGF-β-mediated up-regulation of COL7A1 expression in HaCaT keratinocytes, suggesting that the combination of TGF-β and TNF-α or IL-1β induces a signaling pathway that is completely different from that induced by either pro-inflammatory cytokine alone.