Role of TIPE2 in endogenous protective mechanism of acute lung injury in septic mice: the relationship with TAK1/p38 MAPK/NF-κB signaling pathway / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of tumor necrosis factor-alpha-induced protein-8 like-2 (TIPE2) in endogenous protective mechanism of acute lung injury (ALI) in septic mice and the relationship with transforming growth factor-β-activated protein kinase (TAK1)/p38-mitogen-activated phosphokinase (p38 MAPK)/nuclear factor κB (NF-κB) signaling pathway.Methods:Sixteen male wild-type mice and 16 TIPE2-knockout mice, aged 6-8 weeks, weighing 20-25 g, were randomly divided into 4 groups wild-type sham operation group (group WT-sham), wild-type ALI group (group WT-ALI), TIPE2-knockout sham operation group (group KO-sham) and TIPE2-knockout ALI group (group KO-ALI), with 8 mice in each group.The ALI model was established by cecal ligation and perforation (CLP) in septic mice.Mice were sacrificed at 24 h after CLP to acquire left carotid artery blood samples and lung tissue sections.Lung tissue sections were stained with hematoxylin & eosin (H&E) to examine the pathological changes and lung injury scores were assessed.Arterial blood samples were collected from the left carotid artery for blood gas analysis, and oxygenation index (OI) was calculated.Bronchoalveolar lavage fluid was collected to measure polymorphonuclear neutrophil (PMN) count.The expression of TIPE2, phosphorylated TAK1 (p-TAK1), phosphorylated p38 MAPK (p-p38) MAPK and phosphorylated NF-κB p65 (p-NF-κB p65) was detected using Western blot analysis.The levels of interleukin-1beta (IL-1β) and IL-6 in serum were determined by enzyme-linked immunosorbent assay.Results:Compared with group WT-sham, the lung injury score, PMN counts and concentrations of IL-1β and IL-6 in serum were significantly increased, the expression of p-TAK1, p-p38 MAPK and p-NF-κB p65 was up-regulated, the PaO 2 and OI were decreased, and the expression of TIPE2 was down-regulated in WT-ALI and KO-ALI groups ( P<0.05). Compared with group WT-ALI, the lung injury score, PMN counts and concentrations of IL-1β and IL-6 in serum were significantly increased, the expression of p-TAK1, p-p38 MAPK and p-NF-κB p65 was up-regulated, the PaO 2 and OI were decreased, and the expression of TIPE2 was down-regulated in group KO-ALI ( P<0.05). Conclusion:TIPE2 is involved in the endogenous protective mechanism underlying ALI in septic mice, which is related to inhibiting activation of TAK1/p38 MAPK/NF-κB signaling pathway.