title: Small interfering RNA targeting NF-κB attenuates lipopolysaccharide-induced acute lung injury in rats.
abstract: BACKGROUND
  To investigate the anti-inflammatory effects of specific small interfering RNA targeting NF-κB on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats.
  
  
  METHODS
  Acute lung injury was induced in Sprague-Dawley rats by intraperitoneal injection with LPS (5 mg/kg), followed by immediate intratracheal instillation of siRNA targeting NF-κB p65 (40 μg/ml). Animals in each group were sacrificed at 1 h or 8 h after the instillation. Pulmonary histological changes were evaluated by hematoxylin-eosin staining. The levels of NF-κB and TNF-α were measured by qRT-PCR. Expressions of NF-κB in lung cells and TNF-α in bronchoalveolar lavage fluid (BALF) were determined by western blot analysis and enzyme-linked immunosorbent assay (ELISA) respectively.
  
  
  RESULTS
  LPS administration reduced the rectal temperature and white blood cell counts at 1 h, increased lung wet/dry weight ratios, caused evident lung histopathological injury, and increased the detectable transcript and cytokine levels of TNF-α in lung tissue in BALF. siRNA targeting of NF-κB p65 effectively abrogated the expression of NF-κB p65 in lung cells and, aside from rectal temperatures, ameliorated all changes induced by LPS.
  
  
  CONCLUSIONS
  NF-κB knockdown exerts anti-inflammatory effects on LPS-induced ALI especially in the initial phase, which may be due in part to reduced levels of the proinflammatory cytokine TNF-α. NF-κB siRNA's rapidity and effectiveness to abrogate ALI development may provide an effective therapeutic method with future clinical applications.
authors.affiliation: Department of Neonatology, Dongguan Children Hospital, Guangdong Medical University, Dongguan, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Pediatric Center of Zhujiang Hospital, Southern Medical University, Guangzhou, China.|Yale Cancer Center, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Yuanbin
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Han
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Shuhui
authors.initials: S
authors.lastname: Lin
authors.affiliation: Yale Cancer Center, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Oscar
authors.identifier: http://orcid.org/0000-0002-1182-2662
authors.initials: O
authors.lastname: Ramirez
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China. redsnow007@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002452:Cell Count; D007962:Leukocytes / Q000187:drug effects; D008070:Lipopolysaccharides; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha
keywords: Acute lung injury; Lipopolysaccharide; Nuclear factor-κB; RNA interference