In:
Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 14, No. 638 ( 2022-03-30)
Abstract:
Increasing cyclic adenosine monophosphate (cAMP) in the airways of patients with obstructive lung diseases can reduce airway inflammation and constriction. However, current therapies can induce treatment-limiting systemic side effects. Here, Ghigo and colleagues found that phosphoinositide 3-kinase γ (PI3Kγ) negatively regulated the β 2 -adrenergic receptor signaling pathway to decrease cAMP. They created a PI3Kγ mimetic peptide that increased local cAMP concentrations and, when administered intratracheally in a mouse model of asthma, induced airway relaxation and reduced neutrophil infiltration. Further, in airway epithelial cells from patients with cystic fibrosis, it triggered gating of the cystic fibrosis transmembrane conductance regulator (CFTR) channel and enhanced the effects of CFTR modulators, suggesting that the PI3Kγ mimetic peptide may be used to treat obstructive lung diseases in humans.
Type of Medium:
Online Resource
ISSN:
1946-6234
,
1946-6242
DOI:
10.1126/scitranslmed.abl6328
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2022