Toll-like Receptor 4 Signaling in Ventilator-induced Diaphragm Atrophy
| Autor: | Michiel Vaneker, Leo M. A. Heunks, Marianne Linkels, Johannes G. van der Hoeven, Gert Jan Scheffer, Hieronymus W. H. van Hees, Willem-Jan M. Schellekens, P. N. Richard Dekhuijzen |
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| Přispěvatelé: | Intensive care medicine, ACS - Pulmonary hypertension & thrombosis |
| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_treatment Diaphragm Proinflammatory cytokine Mice Atrophy medicine Animals Pathogenesis and modulation of inflammation [DCN MP - Plasticity and memory N4i 1] Receptor Mechanical ventilation Toll-like receptor Ventilators Mechanical business.industry Autophagy medicine.disease Cell biology Diaphragm (structural system) Pathogenesis and modulation of inflammation [N4i 1] Mice Inbred C57BL Toll-Like Receptor 4 Disease Models Animal Muscular Atrophy Anesthesiology and Pain Medicine Immunology Signal transduction business Poverty-related infectious diseases Aetiology screening and detection [N4i 3] Signal Transduction |
| Zdroj: | Anesthesiology, 117(2), 329-338. Lippincott Williams and Wilkins Anesthesiology, 117, 2, pp. 329-338 Anesthesiology, 117, 329-338 Schellekens, W J M, Van Hees, H W H, Vaneker, M, Linkels, M, Dekhuijzen, P N R, Scheffer, G J, Van Der Hoeven, J G & Heunks, L M A 2012, ' Toll-like receptor 4 signaling in ventilator-induced diaphragm atrophy ', Anesthesiology, vol. 117, no. 2, pp. 329-338 . https://doi.org/10.1097/ALN.0b013e3182608cc0 |
| ISSN: | 0003-3022 |
| Popis: | Background Mechanical ventilation induces diaphragm muscle atrophy, which plays a key role in difficult weaning from mechanical ventilation. The signaling pathways involved in ventilator-induced diaphragm atrophy are poorly understood. The current study investigated the role of Toll-like receptor 4 signaling in the development of ventilator-induced diaphragm atrophy. Methods Unventilated animals were selected for control: wild-type (n = 6) and Toll-like receptor 4 deficient mice (n = 6). Mechanical ventilation (8 h): wild-type (n = 8) and Toll-like receptor 4 deficient (n = 7) mice.Myosin heavy chain content, proinflammatory cytokines, proteolytic activity of the ubiquitin-proteasome pathway, caspase-3 activity, and autophagy were measured in the diaphragm. Results Mechanical ventilation reduced myosin content by approximately 50% in diaphragms of wild-type mice (P less than 0.05). In contrast, ventilation of Toll-like receptor 4 deficient mice did not significantly affect diaphragm myosin content. Likewise, mechanical ventilation significantly increased interleukin-6 and keratinocyte-derived chemokine in the diaphragm of wild-type mice, but not in ventilated Toll-like receptor 4 deficient mice. Mechanical ventilation increased diaphragmatic muscle atrophy factor box transcription in both wild-type and Toll-like receptor 4 deficient mice. Other components of the ubiquitin-proteasome pathway and caspase-3 activity were not affected by ventilation of either wild-type mice or Toll-like receptor 4 deficient mice. Mechanical ventilation induced autophagy in diaphragms of ventilated wild-type mice, but not Toll-like receptor 4 deficient mice. Conclusion Toll-like receptor 4 signaling plays an important role in the development of ventilator-induced diaphragm atrophy, most likely through increased expression of cytokines and activation of lysosomal autophagy. |
| Databáze: | OpenAIRE |
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