Ventilator-induced lung injury is mediated by the NLRP3 inflammasome

The innate immune response is important in ventilator-induced lung injury (VILI) but the exact pathways involved are not elucidated. The authors studied the role of the intracellular danger sensor NLRP3 inflammasome. NLRP3 inflammasome gene expression was analyzed in respiratory epithelial cells and...

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Vydáno v:Anesthesiology (Philadelphia) Ročník 116; číslo 5; s. 1104
Hlavní autoři: Kuipers, Maria T, Aslami, Hamid, Janczy, John R, van der Sluijs, Koenraad F, Vlaar, Alexander P J, Wolthuis, Esther K, Choi, Goda, Roelofs, Joris J T H, Flavell, Richard A, Sutterwala, Fayyaz S, Bresser, Paul, Leemans, Jaklien C, van der Poll, Tom, Schultz, Marcus J, Wieland, Catharina W
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.05.2012
Témata:
Animals
Bronchoalveolar Lavage Fluid - chemistry
Carrier Proteins - genetics
Carrier Proteins - physiology
Caspase 1 - metabolism
Cytokines - blood
Cytokines - metabolism
Enzyme Activation - physiology
Epithelial Cells - metabolism
Glyburide - pharmacology
Humans
Inflammasomes - genetics
Macrophages, Alveolar - metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Neutrophil Infiltration
NLR Family, Pyrin Domain-Containing 3 Protein
Organ Size - physiology
Receptors, Interleukin-1 - antagonists & inhibitors
Respiration, Artificial
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Tidal Volume - physiology
Up-Regulation - physiology
Uric Acid - metabolism
Ventilator-Induced Lung Injury - genetics
Ventilator-Induced Lung Injury - pathology
ISSN:1528-1175, 1528-1175
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Shrnutí:The innate immune response is important in ventilator-induced lung injury (VILI) but the exact pathways involved are not elucidated. The authors studied the role of the intracellular danger sensor NLRP3 inflammasome. NLRP3 inflammasome gene expression was analyzed in respiratory epithelial cells and alveolar macrophages obtained from ventilated patients (n = 40). In addition, wild-type and NLRP3 inflammasome deficient mice were randomized to low tidal volume (approximately 7.5 ml/kg) and high tidal volume (approximately 15 ml/kg) ventilation. The presence of uric acid in lung lavage, activation of caspase-1, and NLRP3 inflammasome gene expression in lung tissue were investigated. Moreover, mice were pretreated with interleukin-1 receptor antagonist, glibenclamide, or vehicle before start of mechanical ventilation. VILI endpoints were relative lung weights, total protein in lavage fluid, neutrophil influx, and pulmonary and systemic cytokine and chemokine concentrations. Data represent mean ± SD. Mechanical ventilation up-regulated messenger RNA expression levels of NLRP3 in alveolar macrophages (1.0 ± 0 vs. 1.70 ± 1.65, P less than 0.05). In mice, mechanical ventilation increased both NLRP3 and apoptosis-associated speck-like protein messenger RNA levels, respectively (1.08 ± 0.55 vs. 3.98 ± 2.89; P less than 0.001 and 0.95 ± 0.53 vs. 6.0 ± 3.55; P less than 0.001), activated caspase-1, and increased uric acid levels (6.36 ± 1.85 vs. 41.9 ± 32.0, P less than 0.001). NLRP3 inflammasome deficient mice displayed less VILI due to high tidal volume mechanical ventilation compared with wild-type mice. Furthermore, treatment with interleukin-1 receptor antagonist or glibenclamide reduced VILI. Mechanical ventilation induced a NLRP3 inflammasome dependent pulmonary inflammatory response. NLRP3 inflammasome deficiency partially protected mice from VILI.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1528-1175
1528-1175
DOI:10.1097/ALN.0b013e3182518bc0