title: Losartan attenuated lipopolysaccharide-induced lung injury by suppression of lectin-like oxidized low-density lipoprotein receptor-1.
abstract: BACKGROUND
  Recent study has shown that renin-angiotensin system plays an important role in the development of acute lung injury (ALI) with high level of angiotensin II (AngII) generated form AngI catalyzed by angiotensin-converting enzyme. AngII plays a major effect mainly through AT1 receptor. Therefore, we speculate inhibition of AT1 receptor may possibly attenuate the lung injury. Losartan, an antagonist of AT1 receptor for angiotensin II, attenuated lung injury by alleviation of the inflammation response in ALI, but the mechanism of losartan in ALI still remains unclear.
  
  
  METHODS
  Thirty male Sprague-Dawley rats were randomly divided into Control group, ALI group (LPS), and Losartan group (LPS + Losartan). Bronchoalveolar lavage fluid (BALF) and lung tissue were obtained for analysis. The expressions of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), intercellular adhesion molecule-1 (ICAM-1) and caspase-3 were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting.
  
  
  RESULTS
  In ALI group, TNF-α and protein level in BALF, MPO activity in lung tissue, pulmonary edema and lung injury were significantly increased. Losartan significantly reduced LPS-induced increase in TNF-α and protein level in BALF, MPO activity, pulmonary edema and lung injury in LPS-induced lung injury. The mRNA and protein expression levels of LOX-1 were significantly decreased with the administration of losartan in LPS-induced lung injury. Also, losartan blocked the protein levels of caspase-3 and ICAM-1 mediated by LOX-1 in LPS-induced lung injury.
  
  
  CONCLUSIONS
  Losartan attenuated lung injury by alleviation of the inflammation and cell apoptosis by inhibition of LOX-1 in LPS-induced lung injury.
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Chongqing Medical University Chongqing 40010, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Chongqing Medical University Chongqing 40010, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Chongqing Medical University Chongqing 40010, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Chongqing Medical University Chongqing 40010, China.
authors.forename: Dao-Xin
authors.initials: DX
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Chongqing Medical University Chongqing 40010, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D053148:Caspase 3 / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D015536:Down-Regulation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008070:Lipopolysaccharides; D019808:Losartan / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D017207:Rats, Sprague-Dawley; D051127:Scavenger Receptors, Class E / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000893:Anti-Inflammatory Agents; C000609942:ICAM1 protein, rat; D008070:Lipopolysaccharides; C495136:OLR1 protein, rat; D051127:Scavenger Receptors, Class E; D014409:Tumor Necrosis Factor-alpha; C440499:lipopolysaccharide, Escherichia coli O111 B4; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase; C505410:Casp3 protein, rat; D053148:Caspase 3; D019808:Losartan
keywords: Acute lung injury; caspase-3; intercellular adhesion molecule-1; lectin-like oxidized low-density lipoprotein receptor-1; losartan