title: Inhibition of c-Jun N-terminal Kinase Signaling Pathway Alleviates Lipopolysaccharide-induced Acute Respiratory Distress Syndrome in Rats.
abstract: BACKGROUND
  An acute respiratory distress syndrome (ARDS) is still one of the major challenges in critically ill patients. This study aimed to investigate the effect of inhibiting c-Jun N-terminal kinase (JNK) on ARDS in a lipopolysaccharide (LPS)-induced ARDS rat model.
  
  
  METHODS
  Thirty-six rats were randomized into three groups: control, LPS, and LPS + JNK inhibitor. Rats were sacrificed 8 h after LPS treatment. The lung edema was observed by measuring the wet-to-dry weight (W/D) ratio of the lung. The severity of pulmonary inflammation was observed by measuring myeloperoxidase (MPO) activity of lung tissue. Moreover, the neutrophils in bronchoalveolar lavage fluid (BALF) were counted to observe the airway inflammation. In addition, lung collagen accumulation was quantified by Sircol Collagen Assay. At the same time, the pulmonary histologic examination was performed, and lung injury score was achieved in all three groups.
  
  
  RESULTS
  MPO activity in lung tissue was found increased in rats treated with LPS comparing with that in control (1.26 ± 0.15 U in LPS vs. 0.77 ± 0.27 U in control, P < 0.05). Inhibiting JNK attenuated LPS-induced MPO activity upregulation (0.52 ± 0.12 U in LPS + JNK inhibitor vs. 1.26 ± 0.15 U in LPS, P < 0.05). Neutrophils in BALF were also found to be increased with LPS treatment, and inhibiting JNK attenuated LPS-induced neutrophils increase in BALF (255.0 ± 164.4 in LPS vs. 53 (44.5-103) in control vs. 127.0 ± 44.3 in LPS + JNK inhibitor, P < 0.05). At the same time, the lung injury score showed a reduction in LPS + JNK inhibitor group comparing with that in LPS group (13.42 ± 4.82 vs. 7.00 ± 1.83, P = 0.001). However, the lung W/D ratio and the collagen in BALF did not show any differences between LPS and LPS + JNK inhibitor group.
  
  
  CONCLUSIONS
  Inhibiting JNK alleviated LPS-induced acute lung inflammation and had no effects on pulmonary edema and fibrosis. JNK inhibitor might be a potential therapeutic medication in ARDS, in the context of reducing lung inflammatory.
authors.affiliation: Department of Critical Care Medicine, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Lai
authors.affiliation: Department of Critical Care Medicine, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Chun-Fang
authors.initials: CF
authors.lastname: Qiu
authors.affiliation: Department of Critical Care Medicine, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Chuan-Xi
authors.initials: CX
authors.lastname: Chen
authors.affiliation: Department of Critical Care Medicine, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Min-Ying
authors.initials: MY
authors.lastname: Chen
authors.affiliation: Department of Critical Care Medicine, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Critical Care Medicine, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Guan
authors.affiliation: Department of Critical Care Medicine, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Ouyang
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000627:therapeutic use; D003094:Collagen / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000873:Anthracenes; D008070:Lipopolysaccharides; C432165:pyrazolanthrone; D003094:Collagen; D048031:JNK Mitogen-Activated Protein Kinases