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


CONCLUSIONS
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.
van Meurs
J B
JB
University Hospital Nijmegen, The Netherlands.
van Lent
P L
PL
Singer
I I
II
Bayne
E K
EK
van de Loo
F A
FA
van den Berg
W B
WB
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens; D001168:Arthritis / Q000276:immunology / Q000378:metabolism*; D001861:Bone Regeneration / Q000502:physiology; D002356:Cartilage / Q000737:chemistry / Q000378:metabolism / Q000503:physiopathology; D000939:Epitopes / Q000096:biosynthesis; D007150:Immunohistochemistry; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology; D007719:Knee Joint / Q000737:chemistry / Q000187:drug effects; D008297:Male; D008666:Metalloendopeptidases / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000096:biosynthesis*; D010446:Peptide Fragments / Q000096:biosynthesis*; D011509:Proteoglycans / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012795:Sialoglycoproteins / Q000494:pharmacology*
D000941:Antigens; D000939:Epitopes; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D009842:Oligopeptides; D010446:Peptide Fragments; D011509:Proteoglycans; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; C093378:peptide VDIPEN; D008666:Metalloendopeptidases