title: Lack of the receptor for advanced glycation end-products attenuates E. coli pneumonia in mice.
abstract: BACKGROUND
  The receptor for advanced glycation end-products (RAGE) has been suggested to modulate lung injury in models of acute pulmonary inflammation. To study this further, model systems utilizing wild type and RAGE knockout (KO) mice were used to determine the role of RAGE signaling in lipopolysaccharide (LPS) and E. coli induced acute pulmonary inflammation. The effect of intraperitoneal (i.p.) and intratracheal (i.t.) administration of mouse soluble RAGE on E. coli injury was also investigated.
  
  
  RESULTS
  C57BL/6 wild type and RAGE KO mice received an i.t. instillation of LPS, E. coli, or vehicle control. Some groups also received i.p. or i.t. administration of mouse soluble RAGE. After 24 hours, the role of RAGE expression on inflammation was assessed by comparing responses in wild type and RAGE KO. RAGE protein levels decreased in wild type lung homogenates after treatment with either LPS or bacteria. In addition, soluble RAGE and HMGB1 increased in the BALF after E. coli instillation. RAGE KO mice challenged with LPS had the same degree of inflammation as wild type mice. However, when challenged with E. coli, RAGE KO mice had significantly less inflammation when compared to wild type mice. Most cytokine levels were lower in the BALF of RAGE KO mice compared to wild type mice after E. coli injury, while only monocyte chemotactic protein-1, MCP-1, was lower after LPS challenge. Neither i.p. nor i.t. administration of mouse soluble RAGE attenuated the severity of E. coli injury in wild type mice.
  
  
  CONCLUSIONS
  Lack of RAGE in the lung does not protect against LPS induced acute pulmonary inflammation, but attenuates injury following live E. coli challenge. These findings suggest that RAGE mediates responses to E. coli-associated pathogen-associated molecular pattern molecules other than LPS or other bacterial specific signaling responses. Soluble RAGE treatment had no effect on inflammation.
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Lasse
authors.initials: L
authors.lastname: Ramsgaard
authors.forename: Judson M
authors.initials: JM
authors.lastname: Englert
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Manni
authors.forename: Pavle S
authors.initials: PS
authors.lastname: Milutinovic
authors.forename: Julia
authors.initials: J
authors.lastname: Gefter
authors.forename: Jacob
authors.initials: J
authors.lastname: Tobolewski
authors.forename: Lauren
authors.initials: L
authors.lastname: Crum
authors.forename: Gina M
authors.initials: GM
authors.lastname: Coudriet
authors.forename: Jon
authors.initials: J
authors.lastname: Piganelli
authors.forename: Ruben
authors.initials: R
authors.lastname: Zamora
authors.forename: Yoram
authors.initials: Y
authors.lastname: Vodovotz
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Enghild
authors.forename: Tim D
authors.initials: TD
authors.lastname: Oury
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D054405:Chemokine CCL3 / Q000378:metabolism; D004926:Escherichia coli / Q000472:pathogenicity*; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism; D011014:Pneumonia / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D054405:Chemokine CCL3; D053583:Interleukin-1beta; D015850:Interleukin-6; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D009195:Peroxidase