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- Open Access
IL-1-dependent cartilage damage in a macrophage-driven arthritis model can be circumvented by T cell IL-17
Arthritis Res Ther volume 6, Article number: 30 (2004)
In the murine macrophage-mediated SCW-induced arthritis, IL-1 plays a dominant role in cartilage destruction, as was shown in previous studies using cytokine gene knockout mice or antibodies against IL-1. T cell IL-17 is a proinflammatory cytokine that has many IL-1-like activities. IL-17 is expressed in the synovium of RA patients and may play a role in rheumatoid arthritis (RA) pathology.
In the present study we examined the potency of T cell IL-17 to bypass the relative IL-1 dependency of cartilage damage during macrophage-driven SCW-induced arthritis.
SCW-arthritis was induced in IL-1 deficient mice and their C57Bl/6 controls by intra-articular injection of 25 μg SCW fragments. Sixteen hours before the induction of arthritis, an adenoviral vector expressing murine IL-17 or a control virus was injected into the knee joint. Total knee joints were isolated for histological analysis of joint inflammation by H&E staining and cartilage damage was measured as proteoglycan (PG) depletion by Safranin O staining.
During SCW-induced arthritis, cartilage damage was clearly suppressed in IL-1 deficient mice. Overexpression of T cell IL-17 in the SCW arthritis model caused aggravation of the synovial inflammation and induces more severe PG depletion. IL-1-/- mice showed the same influx of inflammatory cells and comparable degree of cartilage damage as control mice (Fig. 1), indicating that overexpression of IL-17 causes loss of IL-1 dependency in this model.
These data show circumvention of the IL-1 dependency of cartilage damage by T cell IL-17 in the macrophage-driven SCW arthritis model. IL-1 and its receptor share the same signaling pathway through TRAF-6 and NF-κB as IL-17. These data suggest that T cell IL-17 can replace the catabolic function of IL-1 regarding cartilage damage, directly or via interplay with other macrophage-driven factors.
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Koenders, M., Lubberts, E., Joosten, L. et al. IL-1-dependent cartilage damage in a macrophage-driven arthritis model can be circumvented by T cell IL-17. Arthritis Res Ther 6, 30 (2004) doi:10.1186/ar1072
- Rheumatoid Arthritis
- Rheumatoid Arthritis Patient
- Knee Joint
- Adenoviral Vector