title: Rho-kinase inhibitor treatment prevents pulmonary inflammation and coagulation in lipopolysaccharide-induced lung injury.
abstract: BACKGROUND
  In the pathogenesis of sepsis-induced acute lung injury (ALI), the crosstalk between inflammation and coagulation plays a pivotal role. The aim of this study was to investigate the role of Rho kinase (ROCK) inhibitor in alleviating pulmonary inflammation and coagulation in lipopolysaccharide (LPS)-induced acute lung injury (ALI) models.
  
  
  METHODS
  In the in vivo study, mice were randomized to four different groups: Control, Y-27632 (Y), LPS, and LPS+Y-27632 (LPS+Y). ALI was induced by intranasally administering LPS (10μg in 50μL PBS). Y-27632 (10mg/kg body weight,) was injected intraperitoneally at 18h and 1h before LPS challenge. Mice were euthanized at 3h or 8h post LPS challenge (N=8 per group). In the in vitro study, human pulmonary microvascular endothelial cells (HPMECs) were incubated with LPS alone (1μg/mL) or in combination with 10μM Y-27632 or 50μM BAY11-7082. Cells were pretreated with the inhibitors 30min before exposure to LPS. Three hours later, cells were isolated for subsequent analysis.
  
  
  RESULTS
  The myeloperoxidase (MPO) activity and fibrinogen deposits in the lung tissue significantly decreased and the lung damage in ALI mouse was attenuated. Pretreatment with Y-27632 markedly reduced the LPS-induced expression of interleukins 1β and 6, and the activation of nuclear factor (NF)-κB. Furthermore, ROCK inhibitor treatment antagonized the expression of tissue factor (TF) and plasminogen activator inhibitor (PAI)-1 in lung tissue and HPMECs.
  
  
  CONCLUSIONS
  ROCK inhibition protects against the endotoxin-induced pulmonary inflammation and coagulation via NF-kappaB pathway modulation.
authors.affiliation: Department of Intensive Care Unit, The First Hospital of China Medical University, Nanjing Bei Street 155, Shenyang 110001, Liaoning Province, PR China. Electronic address: renyuding@126.com.
authors.forename: Renyu
authors.initials: R
authors.lastname: Ding
authors.affiliation: Department of Intensive Care Unit, The First Hospital of China Medical University, Nanjing Bei Street 155, Shenyang 110001, Liaoning Province, PR China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Intensive Care Unit, The First Hospital of China Medical University, Nanjing Bei Street 155, Shenyang 110001, Liaoning Province, PR China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Intensive Care Unit, The First Hospital of China Medical University, Nanjing Bei Street 155, Shenyang 110001, Liaoning Province, PR China.
authors.forename: Baoyan
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Intensive Care Unit, The First Hospital of China Medical University, Nanjing Bei Street 155, Shenyang 110001, Liaoning Province, PR China. Electronic address: xcma2972@sina.com.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Ma
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000577:Amides / Q000627:therapeutic use*; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D002460:Cell Line; D006801:Humans; D007378:Interleukins / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology; D009570:Nitriles / Q000627:therapeutic use*; D011014:Pneumonia / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D011725:Pyridines / Q000627:therapeutic use*; D013450:Sulfones / Q000627:therapeutic use*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000577:Amides; D007378:Interleukins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009570:Nitriles; D011725:Pyridines; D013450:Sulfones; C108830:Y 27632; D054460:rho-Associated Kinases
keywords: Acute lung injury; Coagulation; Inflammation; Lipopolysaccharide; Nuclear factor-κB; Rho kinase