Details

Autor(en) / Beteiligte

• Zhuo, Xiao-Jun
• Hao, Yu
• Cao, Fei
• Yan, Song-Fan
• Li, Hui
• Wang, Qian
• Cheng, Bi-Huan
• Ying, Bin-Yu
• Smith, Fang Gao
• Jin, Sheng-Wei

Titel

Protectin DX increases alveolar fluid clearance in rats with lipopolysaccharide-induced acute lung injury

Ist Teil von

• Experimental & molecular medicine, 2018-04, Vol.50 (4), p.1-13

Ort / Verlag

United States: Springer Nature B.V

Erscheinungsjahr

2018

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Acute respiratory distress syndrome is a life-threatening critical syndrome resulting largely from the accumulation of and the inability to clear pulmonary edema. Protectin DX, an endogenously produced lipid mediator, is believed to exert anti-inflammatory and pro-resolution effects. Protectin DX (5 µg/kg) was injected i.v. 8 h after LPS (14 mg/kg) administration, and alveolar fluid clearance was measured in live rats (n = 8). In primary rat ATII epithelial cells, protectin DX (3.605 × 10  mg/l) was added to the culture medium with LPS for 6 h. Protectin DX improved alveolar fluid clearance (9.65 ± 1.60 vs. 15.85 ± 1.49, p < 0.0001) and decreased pulmonary edema and lung injury in LPS-induced lung injury in rats. Protectin DX markedly regulated alveolar fluid clearance by upregulating sodium channel and Na, K-ATPase protein expression levels in vivo and in vitro. Protectin DX also increased the activity of Na, K-ATPase and upregulated P-Akt via inhibiting Nedd4-2 in vivo. In addition, protectin DX enhanced the subcellular distribution of sodium channels and Na, K-ATPase, which were specifically localized to the apical and basal membranes of primary rat ATII cells. Furthermore, BOC-2, Rp-cAMP, and LY294002 blocked the increased alveolar fluid clearance in response to protectin DX. Protectin DX stimulates alveolar fluid clearance through a mechanism partly dependent on alveolar epithelial sodium channel and Na, K-ATPase activation via the ALX/PI3K/Nedd4-2 signaling pathway.