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Reduction of interleukin-17-induced inhibition of chondrocyte proteoglycan synthesis in intact murine articular cartilage by interleukin-4.
Arthritis Rheum. 2000 Jun; 43(6):1300-6.AR

Abstract

OBJECTIVE

To investigate the role of interleukin-4 (IL-4) and IL-10 in basal and IL-1- and IL-17-mediated inhibition of chondrocyte metabolism.

METHODS

Cartilage explants of patellae from naive mice were incubated with IL-17 and/or IL-1 alone or were pretreated with IL-4 and IL-10. In addition, knee joints of naive mice were injected intraarticularly with IL-4 and IL-10 alone or were coinjected with IL-1. Chondrocyte proteoglycan (PG) synthesis was measured in intact murine articular cartilage. Levels of nitric oxide (NO) were measured using the Griess reagent.

RESULTS

IL-17, a novel cytokine secreted by CD4+ activated memory T cells, inhibited chondrocyte PG synthesis in intact murine articular cartilage, although the suppressive effect was less potent than that of IL-1. The suppressive effect of IL-17 was completely abolished in the presence of L-NIO (L-NS-[1-iminoethyl]ornithine), an inhibitor of NO metabolism, and IL-17 only slightly induced inhibition of PG synthesis in cartilage explants of patellae from iNOS (inducible NO synthase) knockout mice. This indicates that the suppressive effect of IL-17 was mediated by NO. Pretreatment with IL-4, but not IL-10, significantly reduced the inhibition of chondrocyte PG synthesis induced by IL-1 or IL-17. The IL-4-induced reduction in the inhibitory effects of IL-1 and IL-17 on chondrocyte PG synthesis was accompanied by decreased NO formation in the culture supernatants.

CONCLUSION

IL-17 plays a role in the inhibition of chondrocyte PG synthesis. IL-4 and IL-10 have no effect on basal chondrocyte metabolism. However, IL-4-pretreated cartilage is less sensitive to the suppressive effect of IL-1 as well as IL-17. This suggests that IL-4 is protective in T cell-driven cartilage disturbances, probably through reduction of iNOS.

Authors+Show Affiliations

Department of Rheumatology, University Hospital Nijmegen, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10857788

Citation

Lubberts, E, et al. "Reduction of Interleukin-17-induced Inhibition of Chondrocyte Proteoglycan Synthesis in Intact Murine Articular Cartilage By Interleukin-4." Arthritis and Rheumatism, vol. 43, no. 6, 2000, pp. 1300-6.
Lubberts E, Joosten LA, van de Loo FA, et al. Reduction of interleukin-17-induced inhibition of chondrocyte proteoglycan synthesis in intact murine articular cartilage by interleukin-4. Arthritis Rheum. 2000;43(6):1300-6.
Lubberts, E., Joosten, L. A., van de Loo, F. A., van den Gersselaar, L. A., & van den Berg, W. B. (2000). Reduction of interleukin-17-induced inhibition of chondrocyte proteoglycan synthesis in intact murine articular cartilage by interleukin-4. Arthritis and Rheumatism, 43(6), 1300-6.
Lubberts E, et al. Reduction of Interleukin-17-induced Inhibition of Chondrocyte Proteoglycan Synthesis in Intact Murine Articular Cartilage By Interleukin-4. Arthritis Rheum. 2000;43(6):1300-6. PubMed PMID: 10857788.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduction of interleukin-17-induced inhibition of chondrocyte proteoglycan synthesis in intact murine articular cartilage by interleukin-4. AU - Lubberts,E, AU - Joosten,L A, AU - van de Loo,F A, AU - van den Gersselaar,L A, AU - van den Berg,W B, PY - 2000/6/17/pubmed PY - 2000/7/8/medline PY - 2000/6/17/entrez SP - 1300 EP - 6 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 43 IS - 6 N2 - OBJECTIVE: To investigate the role of interleukin-4 (IL-4) and IL-10 in basal and IL-1- and IL-17-mediated inhibition of chondrocyte metabolism. METHODS: Cartilage explants of patellae from naive mice were incubated with IL-17 and/or IL-1 alone or were pretreated with IL-4 and IL-10. In addition, knee joints of naive mice were injected intraarticularly with IL-4 and IL-10 alone or were coinjected with IL-1. Chondrocyte proteoglycan (PG) synthesis was measured in intact murine articular cartilage. Levels of nitric oxide (NO) were measured using the Griess reagent. RESULTS: IL-17, a novel cytokine secreted by CD4+ activated memory T cells, inhibited chondrocyte PG synthesis in intact murine articular cartilage, although the suppressive effect was less potent than that of IL-1. The suppressive effect of IL-17 was completely abolished in the presence of L-NIO (L-NS-[1-iminoethyl]ornithine), an inhibitor of NO metabolism, and IL-17 only slightly induced inhibition of PG synthesis in cartilage explants of patellae from iNOS (inducible NO synthase) knockout mice. This indicates that the suppressive effect of IL-17 was mediated by NO. Pretreatment with IL-4, but not IL-10, significantly reduced the inhibition of chondrocyte PG synthesis induced by IL-1 or IL-17. The IL-4-induced reduction in the inhibitory effects of IL-1 and IL-17 on chondrocyte PG synthesis was accompanied by decreased NO formation in the culture supernatants. CONCLUSION: IL-17 plays a role in the inhibition of chondrocyte PG synthesis. IL-4 and IL-10 have no effect on basal chondrocyte metabolism. However, IL-4-pretreated cartilage is less sensitive to the suppressive effect of IL-1 as well as IL-17. This suggests that IL-4 is protective in T cell-driven cartilage disturbances, probably through reduction of iNOS. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/10857788/Reduction_of_interleukin_17_induced_inhibition_of_chondrocyte_proteoglycan_synthesis_in_intact_murine_articular_cartilage_by_interleukin_4_ L2 - https://doi.org/10.1002/1529-0131(200006)43:6<1300::AID-ANR12>3.0.CO;2-D DB - PRIME DP - Unbound Medicine ER -