Adenovirus-delivered angiopoietin-1 suppresses NF-κB and p38 MAPK and attenuates inflammatory responses in phosgene-induced acute lung injury.

Abstract

Animals exposed to phosgene (Psg) result in acute lung injury (ALI). We have recently reported that angiopoietin-1 (Ang1) reduces inflammation and vascular hyperpermeability in ALI animals. In this study, we examined whether the beneficial effects of adenovirus-delivered Ang1 (Ad/Ang1) on inflammatory responses in Psg-induced ALI rats are due to the suppression of the nuclear factor-kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) pathways, which play crucial roles in inflammatory responses in ALI. We demonstrated that Psg increased Ang2 and inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-4 (IL-4), IL-6, IL-8, and IL-10, in the serum and bronchoalveolar lavage fluid of ALI rats, determined by ELISA. Ang1 inhibits pro-inflammatory mediators (TNF-α, IL-6 and IL-8) and has no effect on anti-inflammatory mediators (IL-4 and IL-10). Furthermore, the inhibitory action of Ang1 was mediated by the suppression of the NF-κB and p38 MAPK pathways, leading to the attenuation of inflammatory responses of ALI. Thus, Ad/Ang1 may provide a useful tool for the effective treatment in Psg-induced ALI.

• Authors: Dai-Kun He, Yi-Ru Shao, Lin Zhang, Jie Shen, Zhi-Yue Zhong, Jing Wang, Guoxiong Xu
• Journal: Inhalation toxicology (Inhal Toxicol) Vol. 26 Issue 3 Pg. 185-92 (Feb 2014) ISSN: 1091-7691 [Electronic] England
• PMID: 24517841 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiopoietin-1
• Chemical Warfare Agents
• Cytokines
• NF-kappa B
• Phosgene
• p38 Mitogen-Activated Protein Kinases

Topics

• Acute Lung Injury (chemically induced, immunology, prevention & control)
• Adenoviridae
• Angiopoietin-1 (administration & dosage, genetics)
• Animals
• Bronchoalveolar Lavage Fluid (chemistry, cytology, immunology)
• Chemical Warfare Agents (toxicity)
• Cytokines (immunology)
• Drug Delivery Systems
• Genetic Vectors
• Inhalation Exposure
• Male
• NF-kappa B (antagonists & inhibitors, immunology)
• Phosgene (toxicity)
• Rats
• Rats, Sprague-Dawley
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors)