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

作者：He Dai Kun; Shao Yi Ru; Zhang Lin; Shen Jie; Zhong Zhi Yue; Wang Jing; Xu Guoxiong^*

来源：Inhalation Toxicology, 2014, 26(3): 185-192.

DOI：10.3109/08958378.2013.872213

• Acute lung injury
• angiopoietin-1
• cytokine
• NF-kappa B
• p38 MAPK
• phosgene

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-kappa B) 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-alpha (TNF- alpha), 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- alpha, 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-kappa B 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.

• 出版日期2014-2
• 单位复旦大学