Inhibition of PI3K promotes dilation of human small airways in a rho kinase-dependent manner.

ABSTRACT:

Background and purpose

Asthma manifests as a heterogeneous syndrome characterized by airway obstruction, inflammation and hyperresponsiveness (AHR). Although the molecular mechanisms remain unclear, activation of specific PI3K isoforms mediate inflammation and AHR. We aimed to determine whether inhibition of PI3Kδ evokes dilation of airways and to elucidate potential mechanisms.

Experimental approach

Human precision cut lung slices from non-asthma donors and primary human airway smooth muscle (HASM) cells from both non-asthma and asthma donors were utilized. Phosphorylation of Akt, myosin phosphatase target subunit 1 (MYPT1) and myosin light chain (MLC) were assessed in HASM cells following either PI3K inhibitor or siRNA treatment. HASM relaxation was assessed by micro-patte

SUBMITTER: Koziol-White CJ 

PROVIDER: S-EPMC4995285 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature