Allergic airway hyperresponsiveness, inflammation, and remodeling do not develop in phosphoinositide 3-kinase γ–deficient mice

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• 作者：Masahide Takeda ; Wataru Ito ; Masako Tanabe ; Shigeharu Ueki ; Hikari Kato ; Junko Kihara ; Tomomi Tanigai ; Takahito Chiba ; Kazutoshi Yamaguchi ; Hiroyuki Kayaba ; Yumiko Imai ; Kaori Okuyama ; Isao Ohno ; Takehiko Sasaki ; Junichi Chihara
• 关键词：irway hyperresponsiveness ; airway remodeling ; airway inflammation ; asthma ; phosphoinositide 3-kinase γ ; TGF-β ; eosinophil ; migration ; adoptive transfer
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2009
• 出版时间：April 2009
• 年：2009
• 卷：123
• 期：4
• 页码：805-812
• 全文大小：631 K

文摘

Background

Bronchial asthma is characterized by chronic airway inflammation caused by inflammatory cells. Phosphoinositide 3-kinases (PI3Ks) are known to play a prominent role in fundamental cellular responses of various inflammatory cells, including proliferation, differentiation, and cell migration. PI3Ks therefore are expected to have therapeutic potential for asthma. Although some investigations of the involvement between the pathogenesis of asthma and PI3K have been performed, it is unknown whether PI3Kγ, a PI3K isoform, is involved in the pathogenesis of asthma.

Objective

We investigated the role of PI3Kγ in allergen-induced allergic airway inflammation, airway hyperresponsiveness (AHR), and airway remodeling with PI3Kγ-deficient mice.

Methods

After ovalbumin (OVA) sensitization, wild-type (WT) and PI3Kγ-deficient mice were exposed to aerosolized OVA 3 days per week for 5 weeks.

Results

In OVA-sensitized and OVA-challenged (OVA/OVA) PI3Kγ-deficient mice, levels of airway inflammation, AHR, and airway remodeling were significantly decreased compared with those in OVA/OVA WT mice. On the other hand, no significant differences were detected in serum OVA-specific IgE and IgG1 levels and CD4/CD8 balance in bronchoalveolar lavage fluid between OVA/OVA WT mice and OVA/OVA PI3Kγ-deficient mice. To determine in which phase of allergic responses PI3Kγ plays a role, we transferred splenocytes from OVA-sensitized WT or PI3Kγ-deficient mice to naive mice of either genotype. Similar increased levels of eosinophils were induced in both WT recipient mice but not in both PI3Kγ-deficient recipient mice.

Conclusion

PI3Kγ might be involved in allergic airway inflammation, AHR, and airway remodeling by regulating the challenge/effector phase of allergic responses.