Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon-gamma (IFN-gamma) is a lymphokine that activates mononuclear phagocytes. To test the hypothesis that IFN-gamma might have important effects upon the ability of human mononuclear phagocytes to degrade extracellular matrix, we have studied the action of this cytokine on the production of metalloproteinases and the counterregulatory tissue inhibitor of metalloproteinases (TIMP) by the human alveolar macrophage. We have found that IFN-gamma potently and selectively suppresses the lipopolysaccharide-induced production of two metalloproteinases--interstitial collagenase and stromelysin--by 50-90% at doses greater than or equal to 10 U/ml. The synthesis of TIMP and 92-kD type IV collagenase was also diminished by IFN-gamma, but these responses required 50- to 100-fold higher concentrations of the cytokine. All doses of IFN-gamma increased total and secreted protein synthesis slightly, indicating a highly specific effect on metalloenzyme biosynthesis. Inhibition of metalloproteinase expression occurred at a pretranslational level, as evidenced by parallel reductions in enzyme biosynthesis and collagenase-specific steady-state mRNA levels. Interestingly, the effect of IFN-gamma on metalloenzyme production was not readily reversible. Therefore, while IFN-gamma activates the macrophage and renders it tumoricidal, this enhanced function appears to be attained at the expense of the cell's capacity to degrade extracellular matrix.
 ...
PMID:Immune modulation of metalloproteinase production in human macrophages. Selective pretranslational suppression of interstitial collagenase and stromelysin biosynthesis by interferon-gamma. 217 Apr 47

Leukoregulin, a 50-kDa T lymphocyte-derived cytokine, influences the synthesis of collagenase, stromelysin-1, collagen, and hyaluronan in human fibroblasts and is thus a determinant of extracellular matrix economy. We studied the effect of leukoregulin on the expression of plasminogen activator inhibitor type 1 (PAI-1) in human orbital and dermal fibroblasts. The lymphokine upregulated 35S-labeled PAI-1 protein expression in orbital fibroblasts in dose-dependent manner. The effect on extracellular matrix-associated PAI-1 evolved over several hours and was maximal at 10 h, when levels were 75-fold higher than controls, and then fell by 24 h. Leukoregulin treatment increased prostaglandin E2 production in orbital cultures after 24 h. When this increase was blocked with indomethacin, peak PAI-1 levels were maintained. Northern analysis demonstrated a substantial induction of steady-state PAI-1 mRNA levels within 6 h of treatment in orbital cultures. In contrast, leukoregulin lowered PAI-1 protein levels dramatically in skin fibroblasts from the abdominal wall. With regard to PAI-1 expression, it would appear that the anatomic site of origin of fibroblasts is a crucial determinant of the cellular response to leukoregulin.
 ...
PMID:Leukoregulin induces plasminogen activator inhibitor type 1 in human orbital fibroblasts. 765 18