1[alpha],25-Dihydroxyvitamin D.sub.3 Ameliorates Seawater Aspiration-Induced Acute Lung Injury via NF-[kappa]B and RhoA/Rho Kinase Pathways

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Date: Aug. 13, 2014
From: PLoS ONE(Vol. 9, Issue 8)
Publisher: Public Library of Science
Document Type: Article
Length: 6,880 words
Lexile Measure: 1350L

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Abstract :

Introduction Inflammation and pulmonary edema are involved in the pathogenesis of seawater aspiration-induced acute lung injury (ALI). Although several studies have reported that 1[alpha],25-Dihydroxyvitamin D.sub.3 (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-[kappa]B and RhoA/Rho kinase pathways. However, we found that pretreatment with calcitriol significantly inhibited the activation of NF-[kappa]B 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-[kappa]B 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-[kappa]B and RhoA/Rho kinase pathways.

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Gale Document Number: GALE|A418552591