Inhibitory Effect of Gamma Interferon on Cultured Human Keratinocyte Thrombospondin Production, Distribution, and Biologic Activities

Rapidly proliferating keratinocytes (KCs) maintained in low calcium, serum-free medium produce and utilize thrombospondin (TSP) as an attachment and spreading factor. To begin to understand the modulation of KC TSP metabolism, gamma interferon (IFN-γ), a product of activated T lymphocytes, was added to KC cultures. IFN-γ; was chosen because activated T cells appear at sites of cutaneous injury. Two additional cytokines including tumor necrosis factor (TNF) and IFN-β were also examined. IFN-γ (600 U/ml), but not TNF (500 U/ml) or IFN-β (103 U/ml), as single agents decreased KC TSP biosynthesis, secretion, and utilization as an attachment factor. IFN-γ alone did not detectably decrease TSP mRNA levels suggesting a post-transcriptional effect in KCs. However, the combination of IFN-γ (600 U/ml) and TNF (500 U/ml) inhibited TSP mRNA production. These results demonstrate the modulation of KC TSP metabolism and biologic activity