Abstract
We investigated production of plasminogen activator (PA) and cartilage degradation induced by injection of recombinant human interleukin-1 (rhIL-1α) in rabbit knees. Rabbits were injected intra-articularly (i.a.) with 100 ng rhIL-1α and necropsied at 0, 3, 6, 18 and 54 h and synovial lavage and articular cartilage were collected. PA activity in the joint lavage was measured using Z-Lys-thiobenzyl ester as a substrate. Cartilage degradation was assessed by quantitating sulfated glycosaminoglycan (S-GAG) to hydroxyproline (Hyp) and appearance of keratan sulfate (KS) in synovial lavage by and ELISA. The PA activity in the lavage of IL-1 injected knees at 3, 6, and 18 h was elevated 8 to 10 fold compared to vehicle controls. At 54 h the activity declined to approximately one third of that seen at the earlier time points. KS in the joint lavage was highest at 18 h, suggesting proteoglycan degradation. The maximal loss of cartilage proteoglycan (S-GAG/Hyp) occurred by 54 h. These observations demonstrate that i.a. injection of IL-1 stimulated the production of PA activity within the rabbit joint. Since elevation of PA activity is followed by cartilage degradation, we investigated effect of anti-inflammatroy agents on PA activity and cartilage degradation in this model. We found that triamcinolone, indomethacin and dexamethasone were able to suppress PA activity but not the cartilage degradation. These observations suggest that in this model of cartilage degradation suppression of PA is not sufficient to inhibit cartilage degradation.
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References
J.-P. Pujol and G. Loyan,Interleukin-1 and Osteoarthritis. Life Sciences41, 1187–1198 (1987).
Z. Werb, C. Mainardi, C. A. Vater and E. D. Harris,Endogenous activation of latent collagenase by rheumatoid synovial cells. N. Engl. J. Med.296, 017–1023 (1977).
E. R. Pettipher, G. A. Higgs and B. Henderson,Interleukin-1 induces leukocyte infiltration and cartilage proteoglycan degradation in the synovial joint. Proc. Natl. Acad. Sci. (USA)83, 8749–8753 (1986).
E. M. O'Byrne, V. Blancuzzi, D. E. Wilson, M. Wong and A. Y. Jeng, Elevated Substance P and accelerated cartilage degradation in rabbit knees injected with Interleukin-1 and Tumor Necrosis Factor. Arthritis Rheum.33, 1023–1028 (1990).
P. L. Coleman and G. D. J. Green,A coupled photometric assay for plasminogen activator. InMethods in Enzymology. (Ed. L. Lorand) pp. 408–414, Academic Press, New York 1981.
T. Leizer, B. J. Clarris, P. E. Ash, J. van Damme, J. Saklatwala and J. A. Hamilton,Interleukion-1β and Interleukin-1α stimulate the plasminogen activator activity and prostaglandin E2 levels of human synovial cells. Arthrits and Rheum.30, 562–566 (1987).
C. Kettner and E. Shaw,Inactivation of trypsin like enzymes with peptides of arginyl chloromethyl ketone. InMethods in Enzymology (Ed. L. Lorand) pp. 826–842, Academic Press, New York 1981.
E. J.-M. A. Thonar, M. E. Lenz, G. K. Klinsworth, B. Caterson, L. M. Pachman, P. Gilckman, R. Katz, J. Huff and K. E. Keuttner,Quantitation of keratan sulfate in blood as a marker of cartilage catabolism. Arthritis and Rheum.28, 1367–1376 (1986).
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Ganu, V.S., Goldberg, R.L., Blancuzzi, V.J. et al. Elevation of synovial plasminogen activator activity after injection of interleukin-1α into rabbit knee joint. Agents and Actions 34, 226–228 (1991). https://doi.org/10.1007/BF01993287
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DOI: https://doi.org/10.1007/BF01993287