Induction of collagenolytic and proteolytic activities by anti-inflammatory drugs in the skin and fibroblast

Abstract

The administration of cortisol, oxyphenylbutazone and indomethacin to rats results in a marked and abrupt loss of cutaneous collagen from these animals. This collagen loss was associated with the appearance of both collagenolytic and proteolytic activities in the extracellular, extrafibrillar compartment of the skin. Cycloheximide and 5,5-diphenylhydantoin pretreatment inhibited both the cutaneous collagen losses and the appearance of these enzyme activities in the skin. Kinetic studies have shown that within 4 hr after anti-inflammatory drug administration, peak concentrations of both collagenolytic and proteolytic activities were reached in the skin. These enzymatic activities were profoundly depressed by simultaneous administration of puromycin, cycloheximide and actinomycin-D. Monolayers of cultured strain-L fibroblasts neither contained nor released either proteolytic or collagenolytic activities. Within 4 hr after administration of cortisol, idomethacin or oxyphenylbutazone, both types of enzymatic activities appeared within these cell cultures.