EXPRESSION OF COLLAGENASE AND STROMELYSIN IN SKIN FIBROBLASTS FROM RECESSIVE DYSTROPHIC EPIDERMOLYSIS-BULLOSA

Collagenase and stromelysin expression in recessive dystrophic epiderm olysis bullosa (RDEB) was studied at both the protein and the gene exp ression levels in fibroblast cultures. The amount of enzyme protein in the culture medium, as determined using a specific enzyme assay, show ed a 9.7-fold increase in collagenase and a 2.7-fold increase in strom elysin in RDEB fibroblasts (n = 4 patients) compared with controls (n = 3 subjects with normal skin). Collagenase activity was extremely hig h in all RDEB fibroblasts. Gene expression, as assessed by Northern bl ot hybridization, was increased in two sets of RDEB fibroblasts with r espect to collagenase, and in two other sets of RDEB fibroblasts with respect 60 stromelysin. The effect of interleukin-1 alpha (IL-1 alpha) on metalloproteinase expression was also examined. The results reveal ed that: 1) collagenase and stromelysin expression was variably increa sed at both the protein and the gene expression levels in RDEB fibrobl asts; (2) the gene expression level did not always reflect the corresp onding protein level; and (3) IL-1 alpha produced a differential effec t on collagenase and stromelysin expression. Although the causative ge ne for RDEB is a type VII collagen, the abnormal expression of collage nase and/or stromelysin is still important in considering the pathophy siology of RDEB.