The effect of tumor necrosis factor alpha and gamma-interferon on the resorption of human articular cartilage and on the production of prostaglandin E and of caseinase activity by human articular chondrocytes.
In cultured human articular chondrocytes, addition of tumor necrosis factor alpha (TNF alpha) stimulated caseinase activity over the range of 10(-11) M to 10(-7) M and stimulated prostaglandin E (PGE) production over the range of 10(-10) M to 10(-7) M. Maximal stimulation was observed at 10(-8)M TNF alpha for both activities. Gamma-interferon (gamma-IFN) had a variable effect on PGE production and no significant effect on caseinase activity in articular chondrocyte cultures over a concentration range of 0.1-1,000 units/ml. Co-incubation of TNF alpha with gamma-IFN enhanced PGE production and decreased caseinase activity. Concentrations as low as 1 unit/ml of gamma-IFN had significant effects on TNF-stimulated production of PGE and on caseinase activity. Resorption of human articular cartilage was stimulated by TNF alpha (10(-7) M) and was inhibited by gamma-IFN (1,000 units/ml). It is possible that cartilage breakdown in vivo may be modulated by such interactions between cytokines.
Bunning
R A
RA
Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, United Kingdom.
Russell
R G
RG
D002358:Cartilage, Articular / Q000187:drug effects* / Q000201:enzymology; D002478:Cells, Cultured; D003871:Dermatan Sulfate / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D011458:Prostaglandins E / Q000096:biosynthesis*; D011994:Recombinant Proteins; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D011458:Prostaglandins E; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003871:Dermatan Sulfate; D007371:Interferon-gamma; D010447:Peptide Hydrolases; D008666:Metalloendopeptidases; C030895:caseinase; D019278:Matrix Metalloproteinase 3