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

Respiratory Research

Lee-Wei Chen²  Ching-Mei Hsu¹  Hung-Tu Huang³  Ming-Chieh Yang⁴  Yi-An Ko¹ 

[1] Department of Biological Sciences, National Sun Yat-Sen University, 70 Lien-Hai Road, Kaohsiung 804, Taiwan;Institute of Emergency and Critical Care Medicine, National Yang-Ming University, Taipei, Taiwan;Department of Anatomy, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;Department of Surgery, Kaohsiung Veterans General Hospital, Ta-chung 1st Road, Kaohsiung 386, Taiwan

关键词: Chimeric mice;    Alveolar macrophage;    NF-κB;    IL-6;    Inflammation;    Mechanical ventilator;   

Others  :  793200
DOI  :  10.1186/1465-9921-14-69

 received in 2013-03-07, accepted in 2013-06-25,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Ko et al.; licensee BioMed Central Ltd.

【 图 表 】

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