Allergic airway hyperresponsiveness, inflammation, and remodeling do not develop in phosphoinositide 3-kinase gamma-deficient mice.
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 PI3Kgamma, a PI3K isoform, is involved in the pathogenesis of asthma.


OBJECTIVE
We investigated the role of PI3Kgamma in allergen-induced allergic airway inflammation, airway hyperresponsiveness (AHR), and airway remodeling with PI3Kgamma-deficient mice.


METHODS
After ovalbumin (OVA) sensitization, wild-type (WT) and PI3Kgamma-deficient mice were exposed to aerosolized OVA 3 days per week for 5 weeks.


RESULTS
In OVA-sensitized and OVA-challenged (OVA/OVA) PI3Kgamma-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 PI3Kgamma-deficient mice. To determine in which phase of allergic responses PI3Kgamma plays a role, we transferred splenocytes from OVA-sensitized WT or PI3Kgamma-deficient mice to naive mice of either genotype. Similar increased levels of eosinophils were induced in both WT recipient mice but not in both PI3Kgamma-deficient recipient mice.


CONCLUSIONS
PI3Kgamma might be involved in allergic airway inflammation, AHR, and airway remodeling by regulating the challenge/effector phase of allergic responses.
Takeda
Masahide
M
Department of Clinical and Laboratory Medicine, Akita University School of Medicine, Akita, Japan.
Ito
Wataru
W
Tanabe
Masako
M
Ueki
Shigeharu
S
Kato
Hikari
H
Kihara
Junko
J
Tanigai
Tomomi
T
Chiba
Takahito
T
Yamaguchi
Kazutoshi
K
Kayaba
Hiroyuki
H
Imai
Yumiko
Y
Okuyama
Kaori
K
Ohno
Isao
I
Sasaki
Takehiko
T
Chihara
Junichi
J
D000818:Animals; D001249:Asthma / Q000209:etiology*; D001980:Bronchi / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000209:etiology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D058544:Class Ib Phosphatidylinositol 3-Kinase; D016207:Cytokines / Q000032:analysis / Q000502:physiology; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D016130:Immunophenotyping; D007527:Isoenzymes / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D007074:Immunoglobulin G; D007527:Isoenzymes; D007073:Immunoglobulin E; D010047:Ovalbumin; D019869:Phosphatidylinositol 3-Kinases; D058544:Class Ib Phosphatidylinositol 3-Kinase; C546764:Pik3cg protein, mouse