Premium
Tumor necrosis factor bifunctionally regulates matrix metalloproteinases and tissue inhibitor of metalloproteinases (TIMP) production by human fibroblasts
Author(s) -
Ito Akira,
Sato Takashi,
Iga Tatsuya,
Mori Yo
Publication year - 1990
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(90)81127-a
Subject(s) - matrix metalloproteinase , collagenase , tumor necrosis factor alpha , extracellular matrix , tissue inhibitor of metalloproteinase , chemistry , matrix metalloproteinase inhibitor , recombinant dna , metalloproteinase , cytokine , necrosis , microbiology and biotechnology , endocrinology , medicine , biology , enzyme , biochemistry , gene
The production of tissue inhibitor of metalloproteinases (TIMP) in human uterine cervical fibroblasts was increased by human recombinant tumor necrosis factor α (hrTNF) at a low concentration (0.005) but the elevated synthesis was suppressed in a dose‐dependent manner at higher concentrations (up to 50). In contrast, the production of collagenase (EC 3.4.24.7) and stromelysin was stimulated at all the corresponding concentrations. In contrast, human recombinant interleukin‐1α (hrIL‐1, 10) coordinately induced these enzymes and TIMP production. The reduction of the elevated TIMP production by TNF was not due to the inhibition of TIMP secretion. These results suggest that TNF modulates the extracellular matrix degradation in human fibroblasts bifunctionally by the suppression of TIMP production in addition to the acceleration of matrix metalloproteinases production. Furthermore, the fact that TNF and IL‐1 differently controlled the production of TIMP suggests that the signal pathway of TNF for TIMP production is different from that of IL‐1.