Interleukin 6 enhances the production of tissue inhibitor of metalloproteinases (TIMP) but not that of matrix metalloproteinases by human fibroblasts.
We have investigated the effect of interleukin 6 (IL-6) on the synthesis of tissue inhibitor of metalloproteinases (TIMP) and matrix metalloproteinases (MMPs), collagenase (MMP-1) and stromelysin (MMP-3) using human skin and uterine cervical fibroblasts. IL-6 did not modulate the expression of MMPs by these fibroblasts, but the production of TIMP was enhanced by IL-6 in a dose dependent manner, whereas IL-1 stimulated the production of both MMPs and TIMP. The combination of IL-6 and IL-1 further augmented IL-1-induced MMPs and TIMP production. The results provide the first evidence that IL-6 participates in the catabolism of the extracellular matrix components by modulating the effects of IL-1 on MMPs and TIMP synthesis as well as its direct effects on the synthesis of TIMP by connective tissue cells.
Sato
T
T
Department of Biochemistry, Tokyo College of Pharmacy, Japan.
Ito
A
A
Mori
Y
Y
D002478:Cells, Cultured; D017364:Collagenases; D004305:Dose-Response Relationship, Drug; D004792:Enzyme Precursors / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000187:drug effects / Q000201:enzymology*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology*; D006023:Glycoproteins / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology*; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D003012:Microbial Collagenase / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D019714:Tissue Inhibitor of Metalloproteinases
D004792:Enzyme Precursors; D006023:Glycoproteins; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; D008666:Metalloendopeptidases; C022440:procollagenase; D003012:Microbial Collagenase