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Ablation of PDE4B protects from Pseudomonas aeruginosa-induced acute lung injury in mice by ameliorating the cytostorm and associated hypothermia

FASEB J. 2021-09; 
Lina Abou Saleh, Abigail Boyd, Ileana V Aragon, Anna Koloteva, Domenico Spadafora, Wadad Mneimneh, Robert A Barrington, Wito Richter
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Recombinant Antibody Expression … Recombinant mouse TNF-α (#Z02918) and IL-1β (#Z02988) were purchased from GenScript (Piscataway, NJ). Serum cytokines were measured using the LEGENDplex bead array (Mouse inflammation panel, #740150; BioLegend, San Diego, CA) according to the … Get A Quote

摘要

Pseudomonas aeruginosa is a frequent cause of hospital-acquired lung infections characterized by hyperinflammation, antibiotic resistance, and high morbidity/mortality. Here, we show that the genetic ablation of one cAMP-phosphodiesterase 4 subtype, PDE4B, is sufficient to protect mice from acute lung injury induced by P aeruginosa infection as it reduces pulmonary and systemic levels of pro-inflammatory cytokines, as well as pulmonary vascular leakage and mortality. Surprisingly, despite dampening immune responses, bacterial clearance in the lungs of PDE4B-KO mice is significantly improved compared to WT controls. In wildtypes, P aeruginosa-infection produces high systemic levels of several cytokines, includin... More

关键词

Pseudomonas aeruginosa, PDE4B, acute lung injury, cytostorm, hypothermia, interleukin 6