Inhibition of phosphoinositide 3‐kinase δ attenuates allergic airway inflammation and hyperresponsiveness in murine asthma model

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Abstract
P110δ phosphoinositide 3‐kinase (PI3K) plays a pivotal role in the recruitment and activation of certain inflammatory cells. Recent findings revealed that the activity of p110δ also contributes to allergenIgE‐induced mast cell activation and vascular permeability. We investigated the role of p110δ in allergic airway inflammation and hyperresponsiveness using IC87114, a selective p110δ inhibitor, in a mouse asthma model. BALB/c mice were sensitized with OVA and, upon OVA aerosol challenge, developed airway eosinophilia, mucus hypersecretion, elevation in cytokine and chemokine levels, up‐regulation of ICAM‐1 and VCAM‐1 expression, and airway hyperresponsiveness. Intratracheal administration of IC87114 significantly ( P P 4 release into the airspace. Histological studies show that IC87114 inhibited OVA‐induced lung tissue eosinophilia, airway mucus production, and inflammation score. In addition, IC87114 significantly ( P FASEB J. 20, 455–465 (2006)
Funding Information
  • Ministry of Health and Welfare (02-PJ1-PG1CH01-0006)
  • Korea Science and Engineering Foundation (M02-2004-000-10251-0)

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