The pathophysiological roles of PI3Ks and therapeutic potential of selective inhibitors in allergic inflammation.
Phosphoinositide 3-kinases (PI3Ks) are known to be involved in a variety of cellular responses such as cell survival, proliferation, differentiation and cell migration. Recently, PI3Ks have been associated with the pathogenesis of asthma because various immune cells regulate allergic responses. Among the three classes of PI3Ks, the roles of PI3K gamma and PI3K delta in allergic responses have attracted particular attention. In a previous report, allergic airway hyperresponsiveness (AHR), inflammation and airway remodeling in an ovalbumin-induced asthma model were decreased in PI3K gamma-deficient mice compared with wild-type mice. In addition, AHR and inflammation were attenuated by administration of a selective PI3K delta inhibitor in a murine model of asthma. These results indicate that PI3K gamma and PI3K delta may be new therapeutic targets for asthma. However, PI3K gamma and PI3K delta may differ in terms of the mechanism of regulation. In this review, we focus on the roles of PI3K gamma and PI3K delta in the pathogenesis of asthma and discuss the mechanistic differences between PI3K gamma and PI3K delta.
Takeda
Masahide
M
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
Ito
Wataru
W
Tanabe
Masako
M
Ueki
Shigeharu
S
Kihara
Junko
J
Kato
Hikari
H
Tanigai
Tomomi
T
Kayaba
Hiroyuki
H
Sasaki
Takehiko
T
Chihara
Junichi
J
D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000201:enzymology* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors
D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors