title: 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.
authors.affiliation: Department of Neonatology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, 223300, Jiangsu, People's Republic of China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.forename: Sai
authors.initials: S
authors.lastname: Zhao
authors.forename: Huaipin
authors.initials: H
authors.lastname: Cheng
authors.forename: Ping
authors.initials: P
authors.lastname: Ji
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.forename: Zhaofang
authors.initials: Z
authors.lastname: Tian
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000096:biosynthesis*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic
references.citation: Genes Cells. 2004 Feb;9(2):165-74
references.pmid: 15009093
references.citation: Pulm Pharmacol Ther. 2011 Oct;24(5):577-86
references.pmid: 21624488
references.citation: Lab Invest. 2004 Jun;84(6):727-35
references.pmid: 15077123
references.citation: Inflammation. 2012 Aug;35(4):1232-41
references.pmid: 22327862
references.citation: BMC Dev Biol. 2007 Mar 07;7:15
references.pmid: 17343756
references.citation: Proc Am Thorac Soc. 2005;2(3):206-13
references.pmid: 16222039
references.citation: Am J Respir Cell Mol Biol. 2011 Aug;45(2):411-8
references.pmid: 21131443
references.citation: Inflammation. 2012 Dec;35(6):1860-6
references.pmid: 23053725
references.citation: Inflammation. 2013 Dec;36(6):1592-604
references.pmid: 23928875
references.citation: Exp Biol Med (Maywood). 2013 Feb;238(2):242-7
references.pmid: 23576805
references.citation: Am J Physiol Lung Cell Mol Physiol. 2013 Aug 15;305(4):L301-11
references.pmid: 23812632
references.citation: PLoS One. 2012;7(10):e45078
references.pmid: 23110043
references.citation: Biol Neonate. 2000 Nov;78(4):308-14
references.pmid: 11093012
references.citation: Am J Respir Cell Mol Biol. 2006 Jul;35(1):10-9
references.pmid: 16514116
references.citation: J Transl Med. 2011 May 13;9:61
references.pmid: 21569464
references.citation: Pediatr Clin North Am. 2008 Jun;55(3):545-75, ix
references.pmid: 18501754
references.citation: Cell Mol Life Sci. 2009 Dec;66(24):3923-35
references.pmid: 19672558
references.citation: Am J Respir Crit Care Med. 2008 Aug 15;178(4):356-62
references.pmid: 18535257
references.citation: Environ Health Perspect. 2011 Mar;119(3):332-6
references.pmid: 21087909
references.citation: J Biomed Biotechnol. 2010;2010:917108
references.pmid: 20145712
references.citation: Am J Respir Crit Care Med. 2006 May 1;173(9):1008-15
references.pmid: 16456142