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-gamma), a product of activated T lymphocytes, was added to KC cultures. IFN-gamma was chosen because activated T cells appear at sites of cutaneous injury. Two additional cytokines including tumor necrosis factor (TNF) and IFN-beta were also examined. IFN-gamma (600 U/ml), but not TNF (500 U/ml) or IFN-beta (10(3) U/ml), as single agents decreased KC TSP biosynthesis, secretion, and utilization as an attachment factor. IFN-gamma alone did not detectably decrease TSP mRNA levels suggesting a post-transcriptional effect in KCs. However, the combination of IFN-gamma (600 U/ml) and TNF (500 U/ml) inhibited TSP mRNA production. These results demonstrate the modulation of KC TSP metabolism and biologic activity.
Nickoloff
B J
BJ
Departments of Pathology, University of Michigan Medical School, Ann Arbor.
Riser
B L
BL
Mitra
R S
RS
Dixit
V M
VM
Varani
J
J
D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007633:Keratins; D012333:RNA, Messenger / Q000096:biosynthesis; D019699:Thrombospondins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D006023:Glycoproteins; D012333:RNA, Messenger; D019699:Thrombospondins; D014409:Tumor Necrosis Factor-alpha; D007633:Keratins; D007371:Interferon-gamma