NF-κB activation in myeloid cells mediates ventilator-induced lung injury

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• 作者：Yi-An Ko (1)
  Ming-Chieh Yang (2)
  Hung-Tu Huang (3)
  Ching-Mei Hsu (1)
  Lee-Wei Chen (2) (4)
  
• 关键词：Mechanical ventilator ; Inflammation ; IL ; 6 ; NF ; κB ; Alveolar macrophage ; Chimeric mice
• 刊名：Respiratory Research
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：14
• 期：1
• 全文大小：1352KB
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• 作者单位：Yi-An Ko (1)
  Ming-Chieh Yang (2)
  Hung-Tu Huang (3)
  Ching-Mei Hsu (1)
  Lee-Wei Chen (2) (4)
  
  1. Department of Biological Sciences, National Sun Yat-Sen University, 70 Lien-Hai Road, Kaohsiung, 804, Taiwan
  2. Department of Surgery, Kaohsiung Veterans General Hospital, Ta-chung 1st Road, Kaohsiung, 386, Taiwan
  3. Department of Anatomy, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
  4. Institute of Emergency and Critical Care Medicine, National Yang-Ming University, Taipei, Taiwan
  

文摘

Background Although use of the mechanical ventilator is a life-saving intervention, excessive tidal volumes will activate NF-κB in the lung with subsequent induction of lung edema formation, neutrophil infiltration and proinflammatory cytokine/chemokine release. The roles of NF-κB and IL-6 in ventilator-induced lung injury (VILI) remain widely debated. Methods To study the molecular mechanisms of the pathogenesis of VILI, mice with a deletion of IкB kinase in the myeloid cells (IKKβ△mye), IL-6-/- to WT chimeric mice, and C57BL/6 mice (WT) were placed on a ventilator for 6 hr. WT mice were also given an IL-6-blocking antibody to examine the role of IL-6 in VILI. Results Our results revealed that high tidal volume ventilation induced pulmonary capillary permeability, neutrophil sequestration, macrophage drifting as well as increased protein in bronchoalveolar lavage fluid (BALF). IL-6 production and IL-1β, CXCR2, and MIP2 expression were also increased in WT lungs but not in those pretreated with IL-6-blocking antibodies. Further, ventilator-induced protein concentrations and total cells in BALF, as well as lung permeability, were all significantly decreased in IKKβ△mye mice as well as in IL6-/- to WT chimeric mice. Conclusion Given that IKKβ△mye mice demonstrated a significant decrease in ventilator-induced IL-6 production, we conclude that NF-κB–IL-6 signaling pathways induce inflammation, contributing to VILI, and IкB kinase in the myeloid cells mediates ventilator-induced IL-6 production, inflammation, and lung injury.