RAGE/NF-κB pathway mediates lipopolysaccharide-induced inflammation in alveolar type I epithelial cells isolated from neonate rats.

Abstract:

: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.

journal_name

Inflammation

journal_title

Inflammation

authors

Li Y,Wu R,Zhao S,Cheng H,Ji P,Yu M,Tian Z

doi

10.1007/s10753-014-9889-y

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

1623-9

issue

5

eissn

0360-3997

issn

1573-2576

journal_volume

37

pub_type

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