Treatment with GSK143 impairs airway contractility to a similar degree as known inhibitors of smooth muscle contraction.

<p>Precision cut lung slices were prepared from BALB/c mice following HDM (solid bars) or Saline exposure (open bars), and the MCh-induced airway contraction was measured. Airways from HDM-exposed mice showed significantly increased airway contraction compared with Saline-mice in the Veh-treated group (*p< 0.05, n = 12 /group), which was abolished by treatment with GSK143 (# p<0.05, n = 12/group). In the HDM mice (solid bars), incubation of the lung slices for 30 mins with inhibitors of PI3 kinase (50 μM), RhoK (1 μM) and MLCK (30 μM) significantly impaired airway contraction compared with slices incubated with DMSO, the diluent control (λ, p<0.05, n = 9-19/group); impairment of airway contraction was similar to that observed in the GSK143-treated airways. Within the DMSO group, HDM-exposed airways showed significantly increased airway contractility compared with Saline-exposed airways (*p<0.05, n = 9-19/group). In the airways of Saline-mice (open bars), inhibitors of PI3 kinase and RhoK significantly impaired airway contraction compared with DMSO-treated airways (ϕ, p<0.05, Saline group, n = 9-19/group), suggesting that these mediators play a role in maintaining normal airway tone.