Skip to main content
PMC home page
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 2000 Jul;59(7):529–532. doi: 10.1136/ard.59.7.529

Effect of interleukin 17 on proteoglycan degradation in murine knee joints

J Dudler 1, N Renggli-Zulliger 1, N Busso 1, M Lotz 1, A So 1
PMCID: PMC1753181  PMID: 10873962

Abstract

OBJECTIVE—To evaluate the effect of murine interleukin 17 (IL17) on cartilage catabolism and joint inflammation by direct intra-articular injection of the cytokine into murine knee joints.
METHODS—Knees of normal C57 Bl mice were injected once or repeatedly with recombinant IL17 or IL1β. Inflammation was estimated by technetium-99m pertechnetate (99Tc) uptake and histological scoring of tissue sections. Proteoglycan depletion was evaluated by histological scoring of safranin O stained sections. Effects on proteoglycan synthesis were studied by 35SO4 incorporation.
RESULTS—A single intra-articular injection of IL17 (10 ng/knee) produced effects very similar to those of IL1β (10 ng/knee). No inflammation was detected at six or 24 hours by 99Tc uptake. However, safranin O staining showed depletion of proteoglycan at 48 hours. Repeated injections of IL17 induced joint inflammation and cartilage proteoglycan depletion as shown by histological scoring. Unlike IL1β, proteoglycan depletion induced by IL17 seemed to be the result of increased degradation only, as no suppression of 35SO4 incorporation was seen.
CONCLUSION—These findings confirm, in vivo, the catabolic effects of IL17 on cartilage. IL17 is thus the first T cell cytokine showing a direct catabolic effect on cartilage in addition to stimulatory effects on macrophages and synoviocytes, making it a potentially important cytokine in the pathogenesis of arthritis.



Full Text

The Full Text of this article is available as a PDF (178.4 KB).

Figure 1  .

Figure 1  

Open in a new tab

Histological changes induced by intra-articular cytokine injection. Knee joints were harvested 24 hours after the last cytokine injection. Standard 7.5 µm paraffin embedded saggital knee sections were stained with safranin O, fast green, and Weighert's haematoxylin (×40). (A and C) Control knees, minimum inflammation and proteoglycan depletion; (B and D) moderate to severe inflammation with infiltration and exudation and proteoglycan depletion in an interleukin 17 injected knee.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aarvak T., Chabaud M., Miossec P., Natvig J. B. IL-17 is produced by some proinflammatory Th1/Th0 cells but not by Th2 cells. J Immunol. 1999 Feb 1;162(3):1246–1251. [PubMed] [Google Scholar]
  2. Attur M. G., Patel R. N., Abramson S. B., Amin A. R. Interleukin-17 up-regulation of nitric oxide production in human osteoarthritis cartilage. Arthritis Rheum. 1997 Jun;40(6):1050–1053. doi: 10.1002/art.1780400609. [DOI] [PubMed] [Google Scholar]
  3. Chabaud M., Durand J. M., Buchs N., Fossiez F., Page G., Frappart L., Miossec P. Human interleukin-17: A T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum. 1999 May;42(5):963–970. doi: 10.1002/1529-0131(199905)42:5<963::AID-ANR15>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
  4. Chabaud M., Fossiez F., Taupin J. L., Miossec P. Enhancing effect of IL-17 on IL-1-induced IL-6 and leukemia inhibitory factor production by rheumatoid arthritis synoviocytes and its regulation by Th2 cytokines. J Immunol. 1998 Jul 1;161(1):409–414. [PubMed] [Google Scholar]
  5. Dolhain R. J., van der Heiden A. N., ter Haar N. T., Breedveld F. C., Miltenburg A. M. Shift toward T lymphocytes with a T helper 1 cytokine-secretion profile in the joints of patients with rheumatoid arthritis. Arthritis Rheum. 1996 Dec;39(12):1961–1969. doi: 10.1002/art.1780391204. [DOI] [PubMed] [Google Scholar]
  6. Fossiez F., Djossou O., Chomarat P., Flores-Romo L., Ait-Yahia S., Maat C., Pin J. J., Garrone P., Garcia E., Saeland S. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J Exp Med. 1996 Jun 1;183(6):2593–2603. doi: 10.1084/jem.183.6.2593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jovanovic D. V., Di Battista J. A., Martel-Pelletier J., Jolicoeur F. C., He Y., Zhang M., Mineau F., Pelletier J. P. IL-17 stimulates the production and expression of proinflammatory cytokines, IL-beta and TNF-alpha, by human macrophages. J Immunol. 1998 Apr 1;160(7):3513–3521. [PubMed] [Google Scholar]
  8. Kennedy J., Rossi D. L., Zurawski S. M., Vega F., Jr, Kastelein R. A., Wagner J. L., Hannum C. H., Zlotnik A. Mouse IL-17: a cytokine preferentially expressed by alpha beta TCR + CD4-CD8-T cells. J Interferon Cytokine Res. 1996 Aug;16(8):611–617. doi: 10.1089/jir.1996.16.611. [DOI] [PubMed] [Google Scholar]
  9. Kotake S., Udagawa N., Takahashi N., Matsuzaki K., Itoh K., Ishiyama S., Saito S., Inoue K., Kamatani N., Gillespie M. T. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest. 1999 May;103(9):1345–1352. doi: 10.1172/JCI5703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lens J. W., van den Berg W. B., van de Putte L. B. Quantitation of arthritis by 99mTc-uptake measurements in the mouse knee-joint: correlation with histological joint inflammation scores. Agents Actions. 1984 Jun;14(5-6):723–728. doi: 10.1007/BF01978915. [DOI] [PubMed] [Google Scholar]
  11. Miossec P., van den Berg W. Th1/Th2 cytokine balance in arthritis. Arthritis Rheum. 1997 Dec;40(12):2105–2115. doi: 10.1002/art.1780401203. [DOI] [PubMed] [Google Scholar]
  12. Rouvier E., Luciani M. F., Mattéi M. G., Denizot F., Golstein P. CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene. J Immunol. 1993 Jun 15;150(12):5445–5456. [PubMed] [Google Scholar]
  13. Shalom-Barak T., Quach J., Lotz M. Interleukin-17-induced gene expression in articular chondrocytes is associated with activation of mitogen-activated protein kinases and NF-kappaB. J Biol Chem. 1998 Oct 16;273(42):27467–27473. doi: 10.1074/jbc.273.42.27467. [DOI] [PubMed] [Google Scholar]
  14. Van bezooijen R. L., Farih-Sips H. C., Papapoulos S. E., Löwik C. W. Interleukin-17: A new bone acting cytokine in vitro. J Bone Miner Res. 1999 Sep;14(9):1513–1521. doi: 10.1359/jbmr.1999.14.9.1513. [DOI] [PubMed] [Google Scholar]
  15. Yao Z., Fanslow W. C., Seldin M. F., Rousseau A. M., Painter S. L., Comeau M. R., Cohen J. I., Spriggs M. K. Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor. Immunity. 1995 Dec;3(6):811–821. doi: 10.1016/1074-7613(95)90070-5. [DOI] [PubMed] [Google Scholar]
  16. Yao Z., Painter S. L., Fanslow W. C., Ulrich D., Macduff B. M., Spriggs M. K., Armitage R. J. Human IL-17: a novel cytokine derived from T cells. J Immunol. 1995 Dec 15;155(12):5483–5486. [PubMed] [Google Scholar]
  17. Yao Z., Spriggs M. K., Derry J. M., Strockbine L., Park L. S., VandenBos T., Zappone J. D., Painter S. L., Armitage R. J. Molecular characterization of the human interleukin (IL)-17 receptor. Cytokine. 1997 Nov;9(11):794–800. doi: 10.1006/cyto.1997.0240. [DOI] [PubMed] [Google Scholar]
  18. de Vries B. J., van den Berg W. B., Vitters E., van de Putte L. B. Quantitation of glycosaminoglycan metabolism in anatomically intact articular cartilage of the mouse patella: in vitro and in vivo studies with 35S-sulfate, 3H-glucosamine, and 3H-acetate. Rheumatol Int. 1986;6(6):273–281. doi: 10.1007/BF00541319. [DOI] [PubMed] [Google Scholar]
  19. van Beuningen H. M., Arntz O. J., van den Berg W. B. In vivo effects of interleukin-1 on articular cartilage. Prolongation of proteoglycan metabolic disturbances in old mice. Arthritis Rheum. 1991 May;34(5):606–615. doi: 10.1002/art.1780340513. [DOI] [PubMed] [Google Scholar]
  20. van de Loo A. A., van Beuningen H. M., van Lent P. L., van den Berg W. B. Direct effect of murine rIL-1 on cartilage metabolism in vivo. Agents Actions. 1989 Jan;26(1-2):153–155. doi: 10.1007/BF02126590. [DOI] [PubMed] [Google Scholar]
  21. van de Loo A. A., van den Berg W. B. Effects of murine recombinant interleukin 1 on synovial joints in mice: measurement of patellar cartilage metabolism and joint inflammation. Ann Rheum Dis. 1990 Apr;49(4):238–245. doi: 10.1136/ard.49.4.238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. van den Berg W. B., van de Loo F. A., Zwarts W. A., Otterness I. G. Effects of murine recombinant interleukin 1 on intact homologous articular cartilage: a quantitative and autoradiographic study. Ann Rheum Dis. 1988 Oct;47(10):855–863. doi: 10.1136/ard.47.10.855. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES