Expression of MMP‐9, MMP‐10 and TNF‐α and lack of epithelial MMP‐1 and MMP‐26 characterize pyoderma gangrenosum

Abstract

Pyoderma gangrenosum (PG) is a non-infectious, autoimmune, chronic ulcer of the skin, often co-existing with inflammatory bowel disease (IBD). Matrix metalloproteinases (MMPs) have been implicated as mediators of tissue destruction in chronic cutaneous and intestinal wounds. Twenty-four skin biopsies with clinically and histologically confirmed PG and acute wounds were immunostained for MMP-1, -7, -8, -9, -10 and -26; tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -3 and tumor necrosis factor-alpha (TNF-alpha). MMP-1 was generally expressed by keratinocytes distal from the wound edge, whereas MMP-10 was detected abundantly in the epithelium. MMP-26 was positive in 42% at the migratory front. Abundant stromal expression was evident for MMP-1, -9 and -10, TIMP-1 and -3 and TNF-alpha. In acute wounds, stromal MMP-1, -9 and -10 and TNF-alpha were sparse. Unlike in normally healing cutaneous wounds, MMP-1 and -26 were detected bordering the wound in only a minority of PGs and their lack may thus retard epithelial repair. Particularly, MMP-9 and -10 and TNF-alpha would be suitable therapeutic targets as they may contribute to the degradation of provisional matrices needed for migration in healing wounds. The presence of MMP-1, -9, -10 and -26 in both PG and IBD ulcers may suggest a similar pathogenesis for cutaneous and mucosal inflammation.