Transforming growth factor beta stimulates the production of the tissue inhibitor of metalloproteinases (TIMP) by human synovial and skin fibroblasts.
IL-1 stimulates the secretion of metalloproteinases by a variety of connective tissue cells and is thought to be the primary inducing agent of connective tissue breakdown in rheumatoid arthritis. Transforming growth factor-beta (TGF-beta) is known to be capable of inhibiting the synthesis of metalloproteinases and to be able to partially inhibit interleukin-1 (IL-1) induced cartilage degradation. The present paper examines the ability of TGF-beta to modulate the action of IL-1 on fibroblasts of synovial and skin origin and investigates the secretion of the tissue inhibitor of metalloproteinases (TIMP) by these cells after exposure to TGF-beta and IL-1. The principal findings are that when four out of five fibroblast lines were exposed to TGF-beta and IL-1 in combination they displayed a significant increase in TIMP secretion; furthermore, in two of these cell lines a significant stimulation of TIMP secretion was induced by TGF-beta alone.
Wright
J K
JK
Rheumatology Research Unit, Addenbrooke's Hospital, Cambridge, U.K.
Cawston
T E
TE
Hazleman
B L
BL
D000328:Adult; D002478:Cells, Cultured; D017364:Collagenases; D004792:Enzyme Precursors / Q000378:metabolism; D005260:Female; D005347:Fibroblasts; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008875:Middle Aged; D012867:Skin / Q000166:cytology / Q000201:enzymology*; D013583:Synovial Membrane / Q000201:enzymology*; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D004792:Enzyme Precursors; D006023:Glycoproteins; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D017364:Collagenases; C022440:procollagenase; D003012:Microbial Collagenase