Type VII collagen is the predominant, if not the exclusive, component of the anchoring fibrils. In this study, we have examined the expression of the type VII collagen gene in human skin fibroblasts and keratinocytes in culture by Northern analyses and immunocytochemistry. Type VII collagen gene expression was greatly enhanced in all cell strains studied after stimulation by transforming growth factor-beta (TGF-beta). However, no definitive correlation between the donor age and the magnitude of TGF-beta response could be made. In contrast, the basal expression of the type VII collagen gene was shown to decrease in an age-dependent manner in fibroblasts. The pro-inflammatory cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) were shown to elevate type VII collagen mRNA levels in a dose-dependent manner. This response was inversely related to the donor age of the cell cultures. The attenuated response of cells from older individuals to TNF-alpha and IL-1 beta was specific for type VII collagen gene expression, because, in the same experiments, collagenase gene expression was strongly elevated by the two cytokines. Our data suggest that type VII collagen gene expression is subject to modulation by the cytokine network, which may play a role in controlling anchoring fibril assembly in normal skin and in pathologic conditions characterized by altered deposition of type VII collagen.