, Volume 37, Issue 5, pp 1623–1629 | Cite as

RAGE/NF-κB Pathway Mediates Lipopolysaccharide-Induced Inflammation in Alveolar Type I Epithelial Cells Isolated from Neonate Rats

  • Yuhong Li
  • Rong Wu
  • Sai Zhao
  • Huaipin Cheng
  • Ping Ji
  • Min Yu
  • Zhaofang Tian


Alveolar type I epithelial cells (AECIs) play an important role in the pathogenesis of acute lung injury. The receptor for advanced glycation end-products (RAGEs) is expressed at a high basal level in AECIs, and its soluble isoform is suggested as a marker of AECI injury. However, the molecular mechanism by which RAGE mediates inflammatory injury in AECIs remains elusive. In this study, we established lipopolysaccharide (LPS)-induced inflammation in AECIs isolated from neonate rats as the experimental model and investigated the role of RAGE/NF-κB signaling in mediating inflammatory response in AECIs. We found that LPS increased RAGE expression and the secretion of tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) in AECIs in a dose-dependent manner. Knockdown of RAGE significantly decreased TNF-α and IL-1β levels in conditioned medium of AECIs. Electrophoretic mobility shift assay (EMSA) showed that NF-κB activation was increased in AECIs treated by LPS. However, knockdown of RAGE inhibited both basic and LPS-induced NF-κB activity in AECIs. Finally, NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly reduced LPS-induced upregulation of RAGE expression at both protein and messenger RNA (mRNA) levels in AECIs. Our results suggest that RAGE mediates inflammatory response in AECIs via activating NF-κB, and RAGE/NF-κB pathway presents potential target for the prevention and therapy of acute lung injury.


acute lung injury alveolar type I epithelial cells RAGE NF-κB 



This study was supported by the Talent Fund of Huai’an First Hospital, Nanjing Medical University.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Yuhong Li
    • 1
  • Rong Wu
    • 2
  • Sai Zhao
    • 1
  • Huaipin Cheng
    • 1
  • Ping Ji
    • 1
  • Min Yu
    • 1
  • Zhaofang Tian
    • 1
  1. 1.Department of Neonatology, Huai’an First People’s HospitalNanjing Medical UniversityHuai’anPeople’s Republic of China
  2. 2.Neonatal Medical CenterHuai’an Maternity and Child Health Care HospitalHuai’anPeople’s Republic of China

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