title: 1α,25-dihydroxyvitamin D3 ameliorates seawater aspiration-induced acute lung injury via NF-κB and RhoA/Rho kinase pathways.
abstract: BACKGROUND
  Inflammation and pulmonary edema are involved in the pathogenesis of seawater aspiration-induced acute lung injury (ALI). Although several studies have reported that 1α,25-Dihydroxyvitamin D3 (calcitriol) suppresses inflammation, it has not been confirmed to be effective in seawater aspiration-induced ALI. Thus, we investigated the effect of calcitriol on seawater aspiration-induced ALI and explored the probable mechanism.
  
  
  METHODS
  Male SD rats receiving different doses of calcitriol or not, underwent seawater instillation. Then lung samples were collected at 4 h for analysis. In addition, A549 cells and rat pulmonary microvascular endothelial cells (RPMVECs) were cultured with calcitriol or not and then stimulated with 25% seawater for 40 min. After these treatments, cells samples were collected for analysis.
  
  
  RESULTS
  Results from real-time PCR showed that seawater stimulation up-regulated the expression of vitamin D receptor in lung tissues, A549 cells and RPMVECs. Seawater stimulation also activates NF-κB and RhoA/Rho kinase pathways. However, we found that pretreatment with calcitriol significantly inhibited the activation of NF-κB and RhoA/Rho kinase pathways. Meanwhile, treatment of calcitriol also improved lung histopathologic changes, reduced inflammation, lung edema and vascular leakage.
  
  
  CONCLUSIONS
  These results demonstrated that NF-κB and RhoA/Rho kinase pathways are critical in the development of lung inflammation and pulmonary edema and that treatment with calcitriol could ameliorate seawater aspiration-induced ALI, which was probably through the inhibition of NF-κB and RhoA/Rho kinase pathways.
authors.affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Minlong
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an, PR China; Lung Injury and Repair Center, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Mingqing
authors.initials: M
authors.lastname: Dong
authors.affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an, PR China; Lung Injury and Repair Center, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an, PR China; Lung Injury and Repair Center, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an, PR China; Lung Injury and Repair Center, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an, PR China; Lung Injury and Repair Center, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Faguang
authors.initials: F
authors.lastname: Jin
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002117:Calcitriol / Q000378:metabolism / Q000627:therapeutic use*; D002460:Cell Line; D016207:Cytokines / Q000097:blood; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005070:Evans Blue; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D011015:Pneumonia, Aspiration / Q000150:complications*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D018167:Receptors, Calcitriol / Q000378:metabolism; D012623:Seawater / Q000009:adverse effects*; D015398:Signal Transduction / Q000502:physiology*; D018709:Statistics, Nonparametric; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D017931:DNA Primers; D016328:NF-kappa B; D018167:Receptors, Calcitriol; D005070:Evans Blue; D054460:rho-Associated Kinases; D002117:Calcitriol