Details

Autor(en) / Beteiligte

• van Meurs, Joyce B. J.
• van Lent, Peter L. E. M.
• Singer, Irwin I.
• Bayne, Ellen K.
• van de Loo, Fons A. J.
• van den Berg, Wim B.

Titel

Interleukin‐1 receptor antagonist prevents expression of the metalloproteinase‐generated neoepitope VDIPEN in antigen‐induced arthritis

Ist Teil von

• Arthritis and rheumatism, 1998-04, Vol.41 (4), p.647-656

Ort / Verlag

New York: John Wiley & Sons, Inc

Erscheinungsjahr

1998

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Objective To investigate the relationship between occurrence of the matrix metalloproteinase‐generated neoepitope VDIPEN and proteoglycan (PG) loss in arthritis, and to examine the role of interleukin‐1 (IL‐1) in VDIPEN expression. Methods VDIPEN expression was investigated in murine antigen‐induced arthritis by immunolocalization studies on joint sections. The involvement of IL‐1 in VDIPEN expression was studied by blocking of IL‐1 using IL‐1 receptor antagonist (IL‐1Ra). Results Profound PG loss was evident early in arthritis, without significant VDIPEN expression. Full expression of the neoepitope appeared after a few days, when PG depletion was severe, and disappeared at late stages when cartilage showed recovery from PG depletion. At sites where chondrocyte death occurred and cartilage did not recover from the initial cartilage depletion, VDIPEN expression remained present. Prophylactic IL‐1Ra treatment of arthritic mice resulted in almost complete prevention of VDIPEN expression. However, IL‐1Ra had only a minor effect on PG depletion, emphasizing that there is no correlation between VDIPEN and early PG depletion. Conclusion This study indicates that IL‐1 is involved in VDIPEN expression. Although VDIPEN‐inducing metalloproteinases do not seem to be involved in early PG depletion during antigen‐induced arthritis, metalloproteinase neoepitopes are present when PG depletion is severe.