1α,25-dihydroxyvitamin D3 ameliorates seawater aspiration-induced acute lung injury via NF-κB and RhoA/Rho kinase pathways.

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 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: Minlong Zhang, Mingqing Dong, Wei Liu, Li Wang, Ying Luo, Zhichao Li, Faguang Jin
• Journal: PloS one (PLoS One) Vol. 9 Issue 8 Pg. e104507 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25118599 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• DNA Primers
• NF-kappa B
• Receptors, Calcitriol
• Evans Blue
• rho-Associated Kinases
• Calcitriol

Topics

• Acute Lung Injury (drug therapy, etiology)
• Analysis of Variance
• Animals
• Blotting, Western
• Calcitriol (metabolism, therapeutic use)
• Cell Line
• Cytokines (blood)
• DNA Primers (genetics)
• Enzyme-Linked Immunosorbent Assay
• Evans Blue
• Humans
• Male
• NF-kappa B (metabolism)
• Pneumonia, Aspiration (complications)
• Rats
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction
• Receptors, Calcitriol (metabolism)
• Seawater (adverse effects)
• Signal Transduction (physiology)
• Statistics, Nonparametric
• rho-Associated Kinases (metabolism)