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

Arthritis and Rheumatism
J B van MeursW B van den Berg

Abstract

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. 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). 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. This study indicates that IL-1 is involved in VDIPEN expression. Although VDIPEN-inducing metalloproteinases do not seem to be involved...Continue Reading

References

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Citations

Dec 4, 1998·Springer Seminars in Immunopathology·W B van den Berg
Feb 10, 2000·The American Journal of Pathology·H SchumannL Bruckner-Tuderman
Apr 1, 2005·Nature·Heather StantonAmanda J Fosang
Sep 17, 2010·The Journal of Biological Chemistry·Wataru AriyoshiWarren Knudson
Oct 18, 2006·Journal of Clinical Rheumatology : Practical Reports on Rheumatic & Musculoskeletal Diseases·Gerald Weissmann
Mar 31, 2005·Molecular and Cellular Biology·Christopher B LittleAmanda J Fosang
Oct 29, 2000·Annals of the Rheumatic Diseases·W B van den Berg
Feb 15, 2001·Arthritis Research·W B van den Berg
Jan 8, 2008·Arthritis Research & Therapy·Raimund W KinneGerd-R Burmester
Oct 24, 2009·Arthritis Research & Therapy·Wim B van den Berg
Nov 30, 2000·Arthritis Research·R W KinneG R Burmester
Aug 10, 2005·Joint, Bone, Spine : Revue Du Rhumatisme·François RannouFrancis Berenbaum
Apr 26, 2005·The Journal of Biological Chemistry·Christopher J PoonAmanda J Fosang
Jan 18, 2018·Glycobiology·Bruce Caterson, James Melrose
May 18, 1999·Current Opinion in Rheumatology·U Müller-LadnerS Gay
Feb 1, 2000·Baillière's Best Practice & Research. Clinical Rheumatology·W B van den Berg, B Bresnihan

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