Tissue Inhibitor of Metalloproteinases (TIMP-1) Stimulates the Secretion of Collagenase from Human Skin Fibroblasts

Abstract This study aimed to investigate possible feedback mechanisms in the control of collagenase (matrix metalloproteinase-1) and tissue inhibitor of metalloproteinases (TIMP-1). Procollagenase, active collagenase, TIMP-1 and collagenase-TIMP complex were applied to human skin and synovial fibroblasts for 48 hours; the cells were washed and the resulting collagenase and TIMP-1 secretion was measured over the following 72 hours using ELISAs. Of the additions, only TIMP-1 showed any measurable effect, stimulating collagenase secretion over a range of 1 - 8 μg/ml. Endotoxin contamination was ruled out as an explanation and the active conformation of the TIMP-1 molecule was shown to be necessary.