title: Small interference RNA targeting TLR4 gene effectively attenuates pulmonary inflammation in a rat model.
abstract: OBJECTIVE
  The present study was to investigate the feasibility of adenovirus-mediated small interference RNA (siRNA) targeting Toll-like receptor 4 (TLR4) gene in ameliorating lipopolysaccharide- (LPS-) induced acute lung injury (ALI).
  
  
  METHODS
  In vitro, alveolar macrophages (AMs) were treated with Ad-siTLR4 and Ad-EFGP, respectively, for 12 h, 24 h, and 48 h, and then with LPS (100 ng/mL) for 2 h, and the function and expression of TLR4 were evaluated. In vivo, rats received intratracheal injection of 300 μL of normal saline (control group), 300 μL of Ad-EGFP (Ad-EGFP group), or 300 μL of Ad-siTLR4 (Ad-siTLR4 group) and then were intravenously treated with LPS (50 mg/kg) to induce ALI.
  
  
  RESULTS
  Ad-siTLR4 treatment significantly reduced TLR4 expression and production of proinflammatory cytokines following LPS treatment both in vitro and in vivo. Significant alleviation of tissue edema, microvascular protein leakage, and neutrophil infiltration was observed in the AdsiTLR4-treated animals.
  
  
  CONCLUSIONS
  TLR4 plays a critical role in LPS-induced ALI, and transfection of Ad-siTLR4 can effectively downregulate TLR4 expression in vitro and in vivo, accompanied by alleviation of LPS-induced lung injury. These findings suggest that TLR4 may serve as a potential target in the treatment of ALI and RNA interfering targeting TLR4 expression represents a therapeutic strategy.
authors.affiliation: Department of Anesthesiology, Eastern Hepatobiliary Hospital, Shanghai, China.
authors.forename: Feixiang
authors.initials: F
authors.lastname: Wu
authors.forename: Yantao
authors.initials: Y
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Lv
authors.forename: Xuerong
authors.initials: X
authors.lastname: Miao
authors.forename: Yuming
authors.initials: Y
authors.lastname: Sun
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yu
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics; D000281:Administration, Intranasal; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D055785:Gene Knockdown Techniques; D008070:Lipopolysaccharides / Q000009:adverse effects; D008168:Lung / Q000737:chemistry / Q000473:pathology; D008297:Male; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D011654:Pulmonary Edema / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051197:Toll-Like Receptor 4