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

48 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
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume296
Issue number2
DOIs
Publication statusPublished - 2009 Feb 1
Externally publishedYes

Fingerprint

Airway Remodeling
Phosphatidylinositol 3-Kinases
Allergens
Inflammation
Ovalbumin
Eosinophils
Chemokine CCL11
Staining and Labeling
Lung
1-Phosphatidylinositol 4-Kinase
Interleukin-5
Bronchoalveolar Lavage
Smooth Muscle
Fibrosis
Collagen
Asthma
Cell Count
Bone Marrow
Epithelial Cells

Keywords

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

ASJC Scopus subject areas

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

Cite this

PI3K7-deficient mice have reduced levels of allergen-induced eosinophilic inflammation and airway remodeling. / Lim, Dae Hyun; Cho, Jae Youn; Song, Dae-Jin; Lee, Sang Yeub; Miller, Marina; Broide, David H.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 296, No. 2, 01.02.2009.

Research output: Contribution to journalArticle

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