Document Detail


Matrix metalloproteinases, IL-6, and nitric oxide in rat antigen-induced arthritis.
MedLine Citation:
PMID:  9631748     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Degradation of extracellular matrix by matrix metalloproteinases (MMPs) is believed to be important in processes leading to the progressive destruction of joints in rheumatoid arthritis (RA). We used the model of antigen-induced arthritis (AIA) to study MMP activity and the influence of cytokines on their expression by synoviocytes. MATERIAL AND METHODS: Procedures used were: mBSA-induced arthritis in rats; investigation of synovial fluids and supernatants of cultured synoviocytes at different time points during AIA; estimation of total MMP activities by fluorescence assay; zymographic investigations; IL-6 bioassay with B9 cells; nitric oxide (NO) estimation. RESULTS: Total MMP activity in the synovial fluids of arthritic joints was higher than in the contralateral joints or in the joints of untreated control animals. The maximum was noted between day 7 and day 14 after arthritis induction. Cultured synoviocytes, prepared at different time points after arthritis induction, secreted MMPs into the media with a maximum time lapse of 14 days after arthritis induction. TNF-alpha increased the total MMP activity released. Moreover, TNF-alpha as well as IL-1 beta induced the expression of MMP9. Finally, TNF-alpha increased the levels of IL-6 and NO in the supernatants of synoviocytes; the extent of stimulation was dependent on the course of AIA. CONCLUSIONS: Different MMPs are synthesized in varying concentrations during the course of rat AIA. Cytokines such as TNF-alpha and IL-1 beta differentially influence the activity and expression of MMPs in cultured synoviocytes. The participation of MMPs in tissue degradation during the course of arthritis may be of importance for the development of new therapeutic strategies.
Authors:
K Mentzel; R Bräuer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental rheumatology     Volume:  16     ISSN:  0392-856X     ISO Abbreviation:  Clin. Exp. Rheumatol.     Publication Date:    1998 May-Jun
Date Detail:
Created Date:  1998-08-24     Completed Date:  1998-08-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8308521     Medline TA:  Clin Exp Rheumatol     Country:  ITALY    
Other Details:
Languages:  eng     Pagination:  269-76     Citation Subset:  IM    
Affiliation:
Institute of Pathology, Friedrich Schiller University Jena, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arthritis, Reactive / enzymology*,  immunology*
Cells, Cultured
Enzyme Activation / drug effects
Female
Gelatin / metabolism
Interleukin-1 / pharmacology
Interleukin-6 / analysis,  immunology,  metabolism*
Male
Metalloendopeptidases / metabolism*
Nitric Oxide / metabolism*
Rats
Rats, Wistar
Synovial Fluid / chemistry,  enzymology
Synovial Membrane / chemistry,  cytology,  enzymology
Tumor Necrosis Factor-alpha / pharmacology
Chemical
Reg. No./Substance:
0/Interleukin-1; 0/Interleukin-6; 0/Tumor Necrosis Factor-alpha; 10102-43-9/Nitric Oxide; 9000-70-8/Gelatin; EC 3.4.24.-/Metalloendopeptidases

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