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

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dc.contributor.authorAlvarez, Diego F.
dc.contributor.authorRenema, Phoibe
dc.contributor.authorHardy, Kierra S.
dc.contributor.authorHousley, Nicole
dc.contributor.authorDunbar, Grace
dc.contributor.authorAnnamdevula, Naga
dc.contributor.authorBritain, Andrea
dc.contributor.authorSpadafora, Domenico
dc.contributor.authorLeavesley, Silas
dc.contributor.authorRich, Thomas
dc.contributor.authorAudia, Jonathon P.
dc.date.accessioned2020-07-08T21:13:39Z
dc.date.available2020-07-08T21:13:39Z
dc.date.issued2020-05-01
dc.description.abstractActivation 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.
dc.description.departmentOsteopathic Medicine
dc.identifier.citationRenema, 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.
dc.identifier.urihttps://hdl.handle.net/20.500.11875/2815
dc.publisherAmerican Journal Physiology Lung Cellular Molecular Physiology
dc.subjectcAMP
dc.subjectcaspase-1
dc.subjectPseudomonas aeraginosa
dc.subjectpulmonary endothelial cells
dc.subjectstress responses
dc.subjectResearch Subject Categoriesen_US
dc.subjectResearch Subject Categoriesen_US
dc.titlecAMP signaling primes lung endothelial cells to activate caspase-1 during Pseudomonas aeruginosa infectionen_US
dc.typeArticleen_US
local.embargo.lift05/2021
local.embargo.terms1 year

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