Figure 4. ADAM10 inhibitor blocks the induction of an IgE/mast cell dependent model potentially through blocking the Th2 response.

Asthma was induced using the IgE-dependent model (Model A). 1 mg/kg in a 20:1 mixture of PBS/DMSO of an ADAM10 inhibitor was injected intranasal every three days throughout the experiment in wild type C57B/6. The control mice (wild type C57B/6) received just the PBS/DMSO mixture. (A) On day 47 AHR was measured using total lung resistance (Significance is between ADAM10 inhibitor treated and LM) and (B) forced oscillation measurements as explained in Fig 3b. Data represents the average of data from at least four sensitized mice and two unsensitized mice. (C) Percentage of BALF cells were determined as in Fig 2a. Shown is the average of at least three animals (same key as B). (D) Total IgE in the serum as determined by ELISA, average of at least four animals. (E) Total IgE in the BALF as determined by ELISA, average of at least three animals. (F) qPCR of total lung RNA was performed using the primers listed in material and methods. Shown is the average of at least five animals. The unsensitized groups were combined, as no difference where seen between them. (G) BALF cytokine levels as determined by multiplex ELISA. Shown is the average of at least five animals per group. Again unsensitized groups were combined. (same key as F). Number above comparison line equals P value, * = P value < .05 and ** = P value <.01