TISSUE INHIBITOR OF METALLOPROTEINASES (TIMP-1) STIMULATES THE SECRETION OF COLLAGENASE FROM HUMAN SKIN FIBROBLASTS

This study aimed to investigate possible feedback mechanisms in the co ntrol of collagenase (matrix metalloproteinase-1) and tissue inhibitor of metalloproteinases (TIMP-1). Procollagenase, active collagenase, T IMP-1 and collagenase-TIMP complex were applied to human skin and syno vial fibroblasts for 48 hours; the cells were washed and the resulting collagenase and TIMP-1 secretion was measured over the following 72 h ours using ELISAs. Of the additions, only TIMP-1 showed any measurable effect, stimulating collagenase secretion over a range of 1 - 8 mu g/ ml. Endotoxin contamination was ruled out as an explanation and the ac tive conformation of the TIMP-1 molecule was shown to be necessary. (C ) 1994 Academic Press, Inc.