Unknown

Dataset Information

0

Pseudomonas aeruginosa Ventilator-Associated Pneumonia Induces Lung Injury through TNF-?/c-Jun NH2-Terminal Kinase Pathways.


ABSTRACT: Ventilator-associated pneumonia (VAP) is a common nosocomial infection among intensive care unit (ICU) patients. Pseudomonas aeruginosa (PA) is the most common multidrug-resistant Gram-negative pathogen and VAP caused by PA carries a high rate of morbidity and mortality. This study examined the molecular mechanism of PA VAP-induced lung injury. C57BL/6 wild-type (WT) mice and JNK1 knockout (JNK1-/-) mice received mechanical ventilation (MV) for 3 h at 2 days after receiving nasal instillation of PA. The WT and JNK1-/- mice also received MV after the induction of lung injury by instillation of supernatants from PA-stimulated alveolar macrophages (AMs). AMs isolated from WT, I?B-kinase (IKK)??Mye (IKK? was selectively deleted in macrophages), and JNK1-/- mice were ex vivo stimulated with live PA and supernatants were collected for cytokine assay. Intranasal instillation of 106 PA enhanced MV-induced NF-?B DNA binding activity in the lungs and nitrite levels in BALF. MV after PA instillation significantly increased the expression of ICAM and VCAM in the lungs and TNF-?, IL-1?, and IL-6 levels in bronchoalveolar lavage fluid (BALF) of WT mice, but not in JNK1-/- mice. MV after supernatant instillation induced more total protein concentration in BALF and neutrophil sequestration in the lungs in WT mice than JNK1-/- mice and cytokine assay of supernatants indicated that TNF-? is a critical regulator of PA VAP-induced lung injury. Ex vivo PA stimulation induced TNF-? production by AMs from WT as well as JNK1-/- mice but not IKK??Mye mice. In summary, PA colonization plays an important role in PA VAP-induced lung injury through the induction of JNK1-mediated inflammation. These results suggest that the pathogenesis mechanism of PA VAP involves production of TNF-? through activation of IKK/NF-?B pathways in AMs and JNK signaling pathway in the lungs.

SUBMITTER: Yang YW 

PROVIDER: S-EPMC5218563 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

altmetric image

Publications

Pseudomonas aeruginosa Ventilator-Associated Pneumonia Induces Lung Injury through TNF-α/c-Jun NH2-Terminal Kinase Pathways.

Yang Ying-Wei YW   Jiang Yu-Zhen YZ   Hsu Ching-Mei CM   Chen Lee-Wei LW  

PloS one 20170106 1


Ventilator-associated pneumonia (VAP) is a common nosocomial infection among intensive care unit (ICU) patients. Pseudomonas aeruginosa (PA) is the most common multidrug-resistant Gram-negative pathogen and VAP caused by PA carries a high rate of morbidity and mortality. This study examined the molecular mechanism of PA VAP-induced lung injury. C57BL/6 wild-type (WT) mice and JNK1 knockout (JNK1-/-) mice received mechanical ventilation (MV) for 3 h at 2 days after receiving nasal instillation of  ...[more]

Similar Datasets

| S-EPMC4725638 | biostudies-other
| S-EPMC2542430 | biostudies-literature
| S-EPMC2546837 | biostudies-other
| S-EPMC7706020 | biostudies-literature
| S-EPMC3957866 | biostudies-other
| S-EPMC2896250 | biostudies-literature
| S-EPMC9112676 | biostudies-literature
| S-EPMC6423012 | biostudies-literature
| S-EPMC6062970 | biostudies-literature
| S-EPMC8846318 | biostudies-literature