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 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 micrograms/ml. Endotoxin contamination was ruled out as an explanation and the active conformation of the TIMP-1 molecule was shown to be necessary.
Clark
I M
IM
Rheumatology Research Unit, Addenbrooke's Hospital, Cambridge, UK.
Powell
L K
LK
Cawston
T E
TE
D002460:Cell Line; D017364:Collagenases / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000032:analysis; D004792:Enzyme Precursors / Q000494:pharmacology; D005246:Feedback; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology*; D006023:Glycoproteins / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D012867:Skin / Q000201:enzymology*; D019714:Tissue Inhibitor of Metalloproteinases
D004731:Endotoxins; D004792:Enzyme Precursors; D006023:Glycoproteins; D007375:Interleukin-1; D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; C022440:procollagenase