Human gelatinase B, a marker enzyme in rheumatoid arthritis, is inhibited by D-penicillamine: anti-rheumatic activity by protease inhibition.
The direct and indirect inhibitory potential of D-penicillamine toward human neutrophil and synovial fluid gelatinase B, a marker enzyme for disease severity in RA, was investigated. Gelatinase and plasminogen activator activities were assessed by SDS-polyacrylamide gel electrophoresis zymography. D-penicillamine significantly inhibits purified and synovial fluid gelatinase B in vitro at concentrations attainable in vivo and also blocks in vitro plasminogen activation. Protease inhibition may be a mechanism of action for D-penicillamine as DMARD.
Norga
K
K
Rega Institute for Medical Research, Leuven, Belgium.
Grillet
B
B
Masure
S
S
Paemen
L
L
Opdenakker
G
G
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000201:enzymology*; D015415:Biomarkers / Q000032:analysis; D017364:Collagenases / Q000187:drug effects / Q000378:metabolism; D000077543:Deferiprone; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020780:Matrix Metalloproteinase 9; D008911:Minocycline / Q000008:administration & dosage / Q000494:pharmacology; D010396:Penicillamine / Q000008:administration & dosage / Q000494:pharmacology*; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000166:cytology
D000900:Anti-Bacterial Agents; D018501:Antirheumatic Agents; D015415:Biomarkers; D011728:Pyridones; D000077543:Deferiprone; D010450:Endopeptidases; D017364:Collagenases; D020780:Matrix Metalloproteinase 9; D008911:Minocycline; D010396:Penicillamine