Figure 6.

Dasatinib inhibits MSU crystal–induced arthritis in vivo. (A– I ) Mice were treated with or without 50 mg/kg dasatinib every 12 h, starting either 1 h prior (A–H) or 4 h after (I) injection of MSU crystals into the hind paws of the experimental animals as described in Figs. 2 and 3. (A, B, and I) Arthritis was followed by measuring paw swelling using a plethysmometer. (C and D) In vivo MPO activity was determined by chemiluminescence imaging. Representative color-coded photon flux intensity superposed on the grayscale photo of the mice (C) and quantified in defined regions of interest (D). (E–H) Analysis of the inflammatory microenvironment by flow cytometry (E) or ELISA (F–H). Panels B–H show results obtained 24 h after MSU crystal injection. Panels C and D show representative color-coded photon flux intensity superposed on the grayscale photo of the mice (C) and quantified in defined regions of interest (D). Kinetic curves and bar graphs show mean and SEM from 9 to 14 (A), 14–24 (B), 7 (D), 4–15 (E–H), and 14–24 (I) mice per group from 3 (A), 2 (D), 3–5 (E–H), and 3–5 (I) independent experiments. Two-way ANOVA inhibitor × stimulus interaction analysis; n.s., not significant; *, P < 0.05; **, P < 0.01; ***, P < 0.001. See the text for actual P values.

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