Influence of proteolytic-antiproteolytic enzymes and prooxidative-antioxidative factors on proteoglycan alterations in children with juvenile idiopathic arthritis.
OBJECTIVE
The influence of proteolytic-antiproteolytic enzymes and prooxidative-anti-oxidative factors on proteoglycan alterations in children with juvenile idiopathic arthritis (JIA) was evaluated in this study.
Plasma and urinary glycosaminoglycans (GAGs), as well as plasma levels of matrix metalloproteinases (MMPs) (MMP-3, MMP-10), tissue inhibitors of metalloproteinases (TIMPs) (TIMP-1, TIMP-2), total oxidative status (TOS) and total antioxidative status (TAS), were quantified in samples obtained from 30 healthy subjects and 30 JIA patients before and after treatment. Significantly decreased plasma and urinary concentration of GAGs in JIA patients before treatment was observed. Therapy resulted in an increase in the concentration of the above listed parameters. However, the plasma GAG level still remained significantly lower compared to that in controls. Increased levels of MMP-3 and TIMP-1 in both JIA patient groups were recorded. The plasma MMP-10 and TIMP-2 concentrations in untreated patients were significantly decreased. Anti-inflammatory treatment led to normalization of these parameter concentrations. Significant increase of TOS but decrease of TAS was found in the blood of untreated patients. The treatment resulted only in the normalization of TOS concentration. We have revealed a significant correlation between plasma GAGs and: MMP-3 (r=0.54), TOS (r=0.64) and urinary GAGs (r=0.55), respectively.


CONCLUSIONS
Proteoglycan/glycosaminoglycan alterations in JIA patients, which are stimulated by MMP-3 and reactive oxygen species (ROS), indicate rather systemic disturbance of extracellular matrix metabolism, and not merely local changes which occur in articular structures. Given the destructive potential of ROS and MMPs and their hyperexpression in JIA, inhibition of these compounds should bring a substantial clinical benefit.
Department of Clinical Chemistry and Laboratory Diagnostics, Medical University of Silesia, ul. Jedności 8, 41-200 Sosnowiec, Poland. Electronic address: winsz@sum.edu.pl.
Katarzyna
K
Winsz-Szczotka
Department of Clinical Chemistry and Laboratory Diagnostics, Medical University of Silesia, ul. Jedności 8, 41-200 Sosnowiec, Poland.
Katarzyna
K
Komosińska-Vassev
Department of Clinical Chemistry and Laboratory Diagnostics, Medical University of Silesia, ul. Jedności 8, 41-200 Sosnowiec, Poland.
Kornelia
K
Kuźnik-Trocha
Department of Rheumatology, The John Paul II Pediatric Center in Sosnowiec, ul. Gabrieli Zapolskiej 3, 41-218 Sosnowiec, Poland.
Anna
A
Gruenpeter
Department of Rheumatology, The John Paul II Pediatric Center in Sosnowiec, ul. Gabrieli Zapolskiej 3, 41-218 Sosnowiec, Poland.
Iwona
I
Lachór-Motyka
Department of Clinical Chemistry and Laboratory Diagnostics, Medical University of Silesia, ul. Jedności 8, 41-200 Sosnowiec, Poland. Electronic address: chem_klin@sum.edu.pl.
Krystyna
K
Olczyk
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism; D001171:Arthritis, Juvenile / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006025:Glycosaminoglycans / Q000097:blood; D006801:Humans; D008297:Male; D053506:Matrix Metalloproteinase 10 / Q000097:blood*; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011509:Proteoglycans / Q000097:blood*; D017382:Reactive Oxygen Species / Q000097:blood; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D006025:Glycosaminoglycans; D011509:Proteoglycans; D017382:Reactive Oxygen Species; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C511770:MMP10 protein, human; D053506:Matrix Metalloproteinase 10
Extracellular matrix remodeling; Juvenile idiopathic arthritis; Matrix metalloproteinases; Oxidative stress; Tissue inhibitors of metalloproteinases