Cigarette smoke up-regulates PDE3 and PDE4 to decrease cAMP in airway cells.

ABSTRACT:

Background and purpose

cAMP is a central second messenger that broadly regulates cell function and can underpin pathophysiology. In chronic obstructive pulmonary disease, a lung disease primarily provoked by cigarette smoke (CS), the activation of cAMP-dependent pathways, via inhibition of hydrolyzing PDEs, is a major therapeutic strategy. Mechanisms that disrupt cAMP signalling in airway cells, in particular regulation of endogenous PDEs, are poorly understood.

Experimental approach

We used a novel Förster resonance energy transfer (FRET) based cAMP biosensor in mice in vivo, ex vivo precision cut lung slices (PCLS) and in human cell models, in vitro, to track the effects of CS exposure.

Key results

Under fenoterol stimulation, FRET responses to cilostamide were sign

SUBMITTER: Zuo H 

PROVIDER: S-EPMC6016635 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature