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Ventilator-induced lung injury is mediated by the NLRP3 inflammasome.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kuipers, Maria Theresa Aslami, Hamid Janczy, John Roger Sluijs, Koenraad F. Van Der Vlaar, Alexander P. J. Wolthuis, Esther K. Choi, Goda C. W. Roelofs, Joris J. T. H. Flavell, Richard A. Sutterwala, Fayyaz Shiraz Bresser, Paul Leemans, Jaklien C. Poll, Tom Van Der Schultz, Marcus J. Wieland, Catharina Wilhelmina |
| Copyright Year | 2012 |
| Abstract | BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS Mechanical ventilation induced a NLRP3 inflammasome dependent pulmonary inflammatory response. NLRP3 inflammasome deficiency partially protected mice from VILI. |
| Starting Page | 24 |
| Ending Page | 28 |
| Page Count | 5 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://anesthesiology.pubs.asahq.org/pdfaccess.ashx?url=/data/journals/jasa/931113/0000542-201205000-00025.pdf |
| PubMed reference number | 22531249v1 |
| Alternate Webpage(s) | https://doi.org/10.1097/ALN.0b013e3182518bc0 |
| DOI | 10.1097/aln.0b013e3182518bc0 |
| Journal | Anesthesiology |
| Volume Number | 116 |
| Issue Number | 5 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Apoptosis Bronchoalveolar Lavage Fluid Caspase-1 Gene Expression Glyburide Immunity, Innate Inflammasomes Interleukin 1 Receptor Antagonist Protein Irrigation Lung Injury Macrophages, Alveolar Mechanical ventilation Milliliter per Kilogram NLRP3 gene Patients RNA Respiration Structure of parenchyma of lung Transcription, Genetic Uric Acid Ventilator - respiratory equipment Weight cytokine inflammatory response neutrophil |
| Content Type | Text |
| Resource Type | Article |
