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Figure 3 | Arthritis Research & Therapy

Figure 3

From: A highly selective, orally active inhibitor of Janus kinase 2, CEP-33779, ablates disease in two mouse models of rheumatoid arthritis

Figure 3

Disease treatment reflected in local paw environment supports the use of a selective JAK2 inhibitor for suppressing joint inflammation. DBA/1 female mice were injected i.v. with purified anti-CII antibodies, then administered 25 μg of LPS i.p. 3 days later to induce arthritis by day 5. Mice that met the arthritis criteria score of 1 per paw were entered into the study. CEP-33779 was administered p.o., b.i.d., throughout the experiment, Dex was administered at 1.5 mg/kg three times weekly i.p., and vehicle (PEG400 + 1% DMSO) was administered p.o. (A) Spleen and paw phospho-STAT3 concentrations were determined by using Luminex bead kits, with the concentrations shown along the y-axis in units per milliliter per 3 mg of total protein as determined by using a bovine serum albumin (BSA) assays. Tissues were removed 2 and 6 hours after administration of CEP-33779 p.o. at 55 mg/kg. Graph shows means ± SEM. *P < 0.05 by two-way ANOVA. (B) Paw phospho-STAT3 expression in CAIA mice over time with CEP-33779 treatment b.i.d. as measured using a Luminex kit. Black arrow indicates treatment start. (C) Paw cytokines were measured as described elsewhere [25]. Mouse 10-plex Luminex kits were used to measure paw cytokines. Cytokines shown include interleukin (IL)-12, interferon γ (IFNγ), IL-2, IL-1β, tumor necrosis factor α (TNFα) and granulocyte macrophage colony-stimulating factor (GM-CSF). Black arrows indicate treatment start. (D) Hematoxylin and eosin-stained, paraffin wax-embedded sections from treated mice show infiltrates and damaged joints. Representative (pathologist-selected) images are shown at × 10 original magnification. Tissues were also stained with Safranin O for matrix degeneration (data not shown). Tissues from five representative mice from each group were sent for histological analysis and graded according to an accepted scoring method (see Materials and methods). All graphs show means ± SEM, and all statistics were calculated using Prism software and two-way ANOVA analysis. *P < 0.05. **P < 0.01. ***P < 0.001. Study size shows n ≥ 10 mice per group and n ≥ 5 mice for individual assays.

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