Inhibition of phosphoinositide 3-kinase delta attenuates XXXX and hyperresponsiveness in @entity19 @entity565 model.

@entity1712 @entity32 @entity59 @entity33518 @entity563 @entity639 @entity19 @entity565 @entity36275 @entity638 @entity6580 @entity58 @entity1312 @entity8024 @entity2710
@entity33518 phosphoinositide 3-kinase (PI3K) plays a pivotal role in the recruitment and activation of certain inflammatory cells. Recent findings revealed that the activity of @entity33518 also contributes to allergen-IgE-induced mast cell activation and vascular permeability. We investigated the role of @entity33518 in @entity32 and hyperresponsiveness using @entity36275 , a selective @entity33518 inhibitor, in a @entity19 @entity565 model. BALB/c @entity19 were sensitized with OVA and, upon OVA aerosol challenge, developed airway @entity1712 , mucus hypersecretion, elevation in cytokine and chemokine levels, up-regulation of @entity8024 and @entity6580 expression, and airway hyperresponsiveness. Intratracheal administration of @entity36275 significantly (P<0.05) attenuated OVA-induced influx into lungs of total leukocytes, eosinophils, neutrophils, and lymphocytes, as well as levels of @entity58 , @entity59 , @entity1312 , and @entity638 in a dose-dependent manner. @entity36275 also significantly (P<0.05) reduced the serum levels of total IgE and OVA-specific IgE and LTC(4) release into the airspace. Histological studies show that @entity36275 inhibited OVA-induced lung tissue @entity1712 , airway mucus production, and @entity32 score. In addition, @entity36275 significantly (P<0.05) suppressed OVA-induced airway hyperresponsiveness to inhaled @entity2710 . Western blot analyses of whole lung tissue lysates shows that @entity36275 markedly attenuated the OVA-induced increase in expression of @entity58 , @entity59 , @entity1312 , @entity8024 , @entity6580 , @entity638 , and @entity639 . Furthermore, @entity36275 treatment markedly attenuated OVA-induced @entity563 phosphorylation of Akt, a downstream effector of PI3K signaling. Taken together, our findings implicate that inhibition of @entity33518 signaling pathway may have therapeutic potential for the treatment of @entity32 .
