1α,25-Dihydroxyvitamin D3 Ameliorates Seawater Aspiration-Induced Lung Injury By Inhibiting The Translocation Of NF-κB and RhoA.
Our previous study have reported that 1α,25-Dihydroxyvitamin D3 (calcitriol) suppresses seawater aspiration-induced ALI in vitro and in vivo. We also have confirmed that treatment with calcitriol ameliorates seawater aspiration-induced inflammation and pulmonary edema via the inhibition of NF-κB and RhoA/Rho kinase pathway activation. In our further work, we investigated the effect of calcitriol on nuclear translocation of NF-κB and membrane translocation of RhoA in vitro. A549 cells and rat pulmonary microvascular endothelial cells (RPMVECs) were cultured with calcitriol or not for 48 h and then stimulated with 25% seawater for 40 min. After these treatments, cells were collected and performed with immunofluorescent staining to observe the translocation of NF-κB and RhoA and the cytoskeleton remodeling. In vitro, seawater stimulation activates nuclear translocation of NF-κB and membrane translocation of RhoA in A549 cells. In addition, seawater administration also induced cytoskeleton remodeling in A549 cells and RPMVECs. However, pretreatment with calcitriol significantly inhibited the activation of NF-κB and RhoA/Rho kinase pathways, as demonstrated by the reduced nuclear translocation of NF-κB and membrane translocation of RhoA in A549 cells. Meanwhile, treatment of calcitriol also regulated the cytoskeleton remodeling in both A549 cells and RPMVECs. These results demonstrated that treatment with calcitriol ameliorates seawater aspiration-induced ALI via inhibition of nuclear translocation of NF-κB and membrane translocation of RhoA and protection of alveolar epithelial and pulmonary microvascular endothelial barrier.
Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, People's Republic of China.
Minlong
M
Zhang
Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, People's Republic of China. jinfag@fmmu.edu.cn.
Faguang
F
Jin
D000072283:A549 Cells; D056809:Alveolar Epithelial Cells / Q000187:drug effects; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000098:blood supply; D055370:Lung Injury / Q000139:chemically induced / Q000188:drug therapy*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D012623:Seawater / Q000009:adverse effects; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*
D016328:NF-kappa B; C118756:dihydroxy-vitamin D3; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D014807:Vitamin D; D020742:rhoA GTP-Binding Protein
1α,25-Dihydroxyvitamin D3; NF-κB; RhoA; acute lung injury; seawater