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Figure 6 | Arthritis Research & Therapy

Figure 6

From: Selective inhibition of spleen tyrosine kinase (SYK) with a novel orally bioavailable small molecule inhibitor, RO9021, impinges on various innate and adaptive immune responses: implications for SYK inhibitors in autoimmune disease therapy

Figure 6

Oral administration of RO9021 abrogated collagen-induced arthritis in mice. (A) Dose-dependent attenuation of clinical scores by RO9021 (n = 14/group). ***P <0.001 compared with vehicle-treated group. po, per orally. (B) Representative toluidine blue-stained paraffin section of hind paws of vehicle (left upper), 5 mg/kg RO9021 (left bottom) and 45 mg/kg RO9021 (right bottom) treated mice. Photomicrograph of naïve mice also shown (right upper). Intense blue staining within joint space (arrows) indicated representative affected joints with inflammation and pannus formation. (C) Histopathological quantitation of inflammation, pannus formation, cartilage damage, and bone resorption in the hind paws of a subgroup of mice (n = 15/group). *P <0.05. (D) Serum level of IL-6 and KC(CXCL1) after 14 days of treatment with vehicle or RO9021. ***P <0.001 compared with vehicle-treated group. (E) Inhibition of anti-IgD induced CD69 expression in ex vivo whole blood assay at 2 and 5 hours post dose, but not at 24 hours post dose. CD69 expression in B220+ cells was induced ex vivo with anti-IgD in terminal whole blood from subgroups of mice. CD69 expression in unstimulated blood (inverted triangle) was also examined and used as baseline control (n = 5/group).

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Arthritis Research & Therapy

ISSN: 1478-6362

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