cAMP signaling primes lung endothelial cells to activate caspase-1 during Pseudomonas aeruginosa infection

Date

2020-05-01

Authors

Alvarez, Diego F.
Renema, Phoibe
Hardy, Kierra S.
Housley, Nicole
Dunbar, Grace
Annamdevula, Naga
Britain, Andrea
Spadafora, Domenico
Leavesley, Silas
Rich, Thomas

Journal Title

Journal ISSN

Volume Title

Publisher

American Journal Physiology Lung Cellular Molecular Physiology

Abstract

Activation of the inflammasome-caspase-1 axis in lung endothelial cells is emerging as a novel arm of the innate immune response to pneumonia and sepsis caused by Pseudomonas aeruginosa. Increased levels of circulating autacoids are hallmarks of pneumonia and sepsis and induce physiological responses via cAMP signaling in targeted cells. However, it is unknown whether cAMP affects other functions, such as P. aeruginosa- induced caspase-1 activation. Herein, we describe the effects of cAMP signaling on caspase-1 activation using a single cell flow cytometry-based assay. P. aeruginosa infection of cultured lung endothelial cells caused caspase-1 activation in a distinct population of cells. Unexpectedly, pharmacological cAMP elevation increased the total number of lung endothelial cells with activated caspase-1. Interestingly, addition of cAMP agonists augmented P. aeruginosa infection of lung endothelial cells as a partial explanation underlying cAMP priming of caspase-1 activation. The cAMP effect(s) appeared to function as a priming signal because addition of cAMP agonists was required either before or early during the onset of infection. However, absolute cAMP levels measured by ELISA were not predictive of cAMP-priming effects. Importantly, inhibition of de novo cAMP synthesis decreased the number of lung endothelial cells with activated caspase-1 during infection. Collectively, our data suggest that lung endothelial cells rely on cAMP signaling to prime caspase-1 activation during P. aeruginosa infection.

Description

Keywords

cAMP, caspase-1, Pseudomonas aeraginosa, pulmonary endothelial cells, stress responses, Research Subject Categories, Research Subject Categories

Citation

Renema, Phoibe, Kierra S. Hardy, Nicole Housley, Grace Dunbar, Naga Annamdevula, Andrea Britain, Domenico Spadafora, et al. “CAMP Signaling Primes Lung Endothelial Cells to Activate Caspase-1 during Pseudomonas Aeruginosa Infection.” American Journal of Physiology-Lung Cellular and Molecular Physiology 318, no. 5 (March 18, 2020): L1074–83. https://doi.org/10.1152/ajplung.00185.2019.