Jbj. Vanmeurs et al., INTERLEUKIN-1 RECEPTOR ANTAGONIST PREVENTS EXPRESSION OF THE METALLOPROTEINASE-GENE RATED NEOEPITOPE VDIPEN IN ANTIGEN-INDUCED ARTHRITIS, Arthritis and rheumatism, 41(4), 1998, pp. 647-656
Objective. To investigate the relationship between occurrence of the m
atrix 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 join
t sections, The involvement of IL-1 in VDIPEN expression was studied b
y blocking of IL-1 using IL-1 receptor antagonist (IL-1Ra), Results, P
rofound PG loss was evident early in arthritis, without significant VD
IPEN expression. Full expression of the neoepitope appeared after a fe
w days, when PG depletion was severe, and disappeared at late stages w
hen cartilage showed recovery from PG depletion. At sites where chondr
ocyte death occurred and cartilage did not recover from the initial ca
rtilage depletion, VDIPEN expression remained present, Prophylactic IL
-1Ra treatment of arthritic mice resulted in almost complete preventio
n 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 inv
olved in VDIPEN expression. Although VDIPEN-inducing metalloproteinase
s do not seem to be involved in early PG depletion during antigen-indu
ced arthritis, metalloproteinase neoepitopes are present when PG deple
tion is severe.