PI3K7-deficient mice have reduced levels of allergen-induced eosinophilic inflammation and airway remodeling

Dae Hyun Lim, Jae Youn Cho, Dae Jin Song, Sang Yeub Lee, Marina Miller, David H. Broide

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

In this study, we have examined the role of phosphoinositide 3 kinase γ (PDKγ), a class Ib PI3K, in contributing to airway remodeling utilizing PI3Kγ-deficient mice exposed to chronic allergen challenge. Wild-type (WT) mice sensitized to ovalbumin (OVA) and chronically challenged with OVA for 1 mo developed significantly increased levels of eosinophilic inflammation and airway remodeling. In contrast, PI3Kγ-deficient mice challenged with OVA had significantly reduced numbers of bronchoalveolar lavage and peribronchial eosinophils compared with WT mice. There was no significant difference in the number of bone marrow or circulating peripheral blood eosinophils when comparing WT mice and PI3Kγ-deficient mice, suggesting that trafficking of eosinophils into the lung was reduced in PI3Kγ-deficient mice. PI3Kγ-deficient and WT mice had similar levels of IL-5 and eotaxin-1. The reduced eosinophil recruitment to the airway in PI3Kγ-deficient mice challenged with OVA was associated with significantly reduced numbers of TGF-β1 + peribronchial cells, reduced numbers of pSmad 2/3 + airway epithelial cells, and pSmad 2/3 + peribronchial cells, as well as significantly reduced levels of peribronchial fibrosis (quanti-tated by trichrome staining and image analysis as well as by lung collagen levels). In addition, the area of peribronchial α-smooth muscle staining was significantly reduced in PI3Kγ-deficient compared with WT mice. Overall, this study demonstrates an important role for PI3Kγ in mediating allergen-induced eosinophilic airway inflammation and airway remodeling, suggesting that PI3Kγ may be a novel therapeutic target in asthma.

Original languageEnglish
Pages (from-to)L210-L219
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume296
Issue number2
DOIs
Publication statusPublished - 2009 Feb 1

Keywords

  • Mucus
  • PSmad2/3
  • Smooth muscle
  • transforming growth factor-β1

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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