Selective tyrosine kinase inhibition by imatinib mesylate for the treatment of autoimmune arthritis
J. Clin. Invest. Ricardo T. Paniagua, et al. 116:2633 doi:10.1172/JCI28546 [
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Figure 3Imatinib inhibits mast cell c-Kit activation and proinflammatory cytokine production. (
A) C1.MC/57.1 mast cells were stimulated with 100 ng/ml SCF in the presence of 0–5 μM imatinib, and after 48 hours culture supernatants were collected and analyzed for TNF-α, GM-CSF, and IL-6 by a bead-based cytokine assay. Values are mean ± SEM. *
P < 0.05, **
P < 0.01 compared with stimulated cells without imatinib. (
B and
C) C1.MC/57.1 mast cells were serum starved, preincubated with imatinib, and stimulated with 100 ng/ml SCF for 10 minutes in the presence or absence of imatinib, and lysates were generated for IB analysis. IBs were probed with antibodies specific for phospho–c-Kit and total c-Kit (
B) and phospho-Akt (Ser473) and total Akt (
C). (
D) Mast cell lysates generated using the stimulation conditions described in
B and
C were printed to generate RPP arrays. RPP arrays were probed with a variety of antibodies specific for phosphorylated (activated) protein tyrosine kinases and levels normalized to levels in unstimulated cells. Yellow represents anti-protein tyrosine kinase antibody reactivity, and blue represents lack of reactivity. (
E) Mast cells are present in CIA synovium. A representative joint section from a mouse with CIA was stained with toluidine blue. Mast cells present in the densely inflamed CIA synovial tissue are indicated by arrows. B, bone; JS, joint space. Original magnification, ×200.
