title: Adiponectin attenuates lipopolysaccharide-induced acute lung injury through suppression of endothelial cell activation.
abstract: Adiponectin (APN) is an adipose tissue-derived factor with anti-inflammatory and vascular protective properties whose levels paradoxically decrease with increasing body fat. In this study, APN's role in the early development of ALI to LPS was investigated. Intratracheal LPS elicited an exaggerated systemic inflammatory response in APN-deficient (APN(-/-)) mice compared with wild-type (wt) littermates. Increased lung injury and inflammation were observed in APN(-/-) mice as early as 4 h after delivery of LPS. Targeted gene expression profiling performed on immune and endothelial cells isolated from lung digests 4 h after LPS administration showed increased proinflammatory gene expression (e.g., IL-6) only in endothelial cells of APN(-/-) mice when compared with wt mice. Direct effects on lung endothelium were demonstrated by APN's ability to inhibit LPS-induced IL-6 production in primary human endothelial cells in culture. Furthermore, T-cadherin-deficient mice that have significantly reduced lung airspace APN but high serum APN levels had pulmonary inflammatory responses after intratracheal LPS that were similar to those of wt mice. These findings indicate the importance of serum APN in modulating LPS-induced ALI and suggest that conditions leading to hypoadiponectinemia (e.g., obesity) predispose to development of ALI through exaggerated inflammatory response in pulmonary vascular endothelium.
authors.affiliation: Pulmonary Center, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Konter
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Parker
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Baez
authors.forename: Stephanie Z
authors.initials: SZ
authors.lastname: Li
authors.forename: Barbara
authors.initials: B
authors.lastname: Ranscht
authors.forename: Martin
authors.initials: M
authors.lastname: Denzel
authors.forename: Frederic F
authors.initials: FF
authors.lastname: Little
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nakamura
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
authors.forename: Alan
authors.initials: A
authors.lastname: Fine
authors.forename: Kenneth
authors.initials: K
authors.lastname: Walsh
authors.forename: Ross S
authors.initials: RS
authors.lastname: Summer
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D052242:Adiponectin / Q000097:blood / Q000172:deficiency / Q000502:physiology; D000818:Animals; D015820:Cadherins / Q000172:deficiency / Q000235:genetics; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000096:biosynthesis; D007442:Intubation, Intratracheal; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008168:Lung / Q000098:blood supply / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011651:Pulmonary Artery / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000093242:Interleukin-6 Inhibitors
chemical_list: D052242:Adiponectin; D015820:Cadherins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000093242:Interleukin-6 Inhibitors; C499919:Adipoq protein, mouse; C099972:H-cadherin; C508600:IL6 protein, human