Unknown

Dataset Information

0

Knockdown of lung phosphodiesterase 2A attenuates alveolar inflammation and protein leak in a two-hit mouse model of acute lung injury.


ABSTRACT: Phosphodiesterase 2A (PDE2A) is stimulated by cGMP to hydrolyze cAMP, a potent endothelial barrier-protective molecule. We previously found that lung PDE2A contributed to a mouse model of ventilator-induced lung injury (VILI). The purpose of the present study was to determine the contribution of PDE2A in a two-hit mouse model of 1-day intratracheal (IT) LPS followed by 4 h of 20 ml/kg tidal volume ventilation. Compared with IT water controls, LPS alone (3.75 ?g/g body wt) increased lung PDE2A mRNA and protein expression by 6 h with a persistent increase in protein through day 4 before decreasing to control levels on days 6 and 10. Similar to the PDE2A time course, the peak in bronchoalveolar lavage (BAL) neutrophils, lactate dehydrogenase (LDH), and protein concentration also occurred on day 4 post-LPS. IT LPS (1 day) and VILI caused a threefold increase in lung PDE2A and inducible nitric oxide synthase (iNOS) and a 24-fold increase in BAL neutrophilia. Compared with a control adenovirus, PDE2A knockdown with an adenovirus expressing a short hairpin RNA administered IT 3 days before LPS/VILI effectively decreased lung PDE2A expression and significantly attenuated BAL neutrophilia, LDH, protein, and chemokine levels. PDE2A knockdown also reduced lung iNOS expression by 53%, increased lung cAMP by nearly twofold, and improved survival from 47 to 100%. We conclude that in a mouse model of LPS/VILI, a synergistic increase in lung PDE2A expression increased lung iNOS and alveolar inflammation and contributed significantly to the ensuing acute lung injury.

SUBMITTER: Rentsendorj O 

PROVIDER: S-EPMC3154628 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

Knockdown of lung phosphodiesterase 2A attenuates alveolar inflammation and protein leak in a two-hit mouse model of acute lung injury.

Rentsendorj Otgonchimeg O   Damarla Mahendra M   Aggarwal Neil R NR   Choi Ji-Young JY   Johnston Laura L   D'Alessio Franco R FR   Crow Michael T MT   Pearse David B DB  

American journal of physiology. Lung cellular and molecular physiology 20110513 2


Phosphodiesterase 2A (PDE2A) is stimulated by cGMP to hydrolyze cAMP, a potent endothelial barrier-protective molecule. We previously found that lung PDE2A contributed to a mouse model of ventilator-induced lung injury (VILI). The purpose of the present study was to determine the contribution of PDE2A in a two-hit mouse model of 1-day intratracheal (IT) LPS followed by 4 h of 20 ml/kg tidal volume ventilation. Compared with IT water controls, LPS alone (3.75 μg/g body wt) increased lung PDE2A mR  ...[more]

Similar Datasets

2009-03-07 | E-GEOD-14431 | biostudies-arrayexpress
2009-03-02 | GSE14431 | GEO
| S-EPMC8250206 | biostudies-literature
| S-EPMC6328369 | biostudies-literature
| S-EPMC6638944 | biostudies-literature
| S-EPMC8649852 | biostudies-literature
| S-EPMC2662943 | biostudies-literature
| S-EPMC3349366 | biostudies-literature
| S-EPMC6099363 | biostudies-literature
| S-EPMC2532979 | biostudies-literature