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

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 mech...

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Bibliographic Details
Published in:Inflammation 2014-10, Vol.37 (5), p.1623-1629
Main Authors: Li, Yuhong, Wu, Rong, Zhao, Sai, Cheng, Huaipin, Ji, Ping, Yu, Min, Tian, Zhaofang
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Biomedical and Life Sciences
Biomedicine
Immunology
Inflammation - chemically induced
Inflammation - metabolism
Internal Medicine
Lipopolysaccharides - toxicity
Lung - drug effects
Lung - metabolism
NF-kappa B - biosynthesis
Pathology
Pharmacology/Toxicology
Pulmonary Alveoli - drug effects
Pulmonary Alveoli - metabolism
Rats
Rats, Sprague-Dawley
Receptor for Advanced Glycation End Products
Receptors, Immunologic - biosynthesis
Respiratory Mucosa - drug effects
Respiratory Mucosa - metabolism
Rheumatology
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Summary: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.
ISSN:0360-3997
1573-2576
DOI:10.1007/s10753-014-9889-y