Role of TIPE2 in endogenous protective mechanism of acute lung injury in septic mice: relationship with TREM-1/NLRP3 inflammasome 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 triggering receptor expressed on myeloid cells-1 (TREM-1)/NOD-like receptor protein 3 (NLRP3) inflammasome signaling pathway.Methods:Twenty male wild-type mice and 20 TIPE2 knockout mice were divided into 4 groups using a random number table method: 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+ CLP group (group KO-ALI), with 10 mice in each group.The ALI model was established by cecal ligation and perforation (CLP) in septic mice.Mice were sacrificed after blood samples were obtained from the abdominal aorta at 24 h after CLP, and lung tissue specimens were obtained for microscopic examination of pathological changes (with a light microscope) which were scored and for determination of wet/dry weight ratio (W/D ratio), myeloperoxidase (MPO) activity, expression of TIPE2, TREM-1, NLRP3, caspase-1 and GSDMD (by Western blot), and concentrations of interleukin-1beta (IL-1β) and IL-18 in serum (by enzyme-linked immunosorbent assay).Results:Compared with group WT-sham, the lung injury score, W/D ratio, MPO activity and concentrations of IL-1β and IL-18 in serum were significantly increased, the expression of TREM-1, NLRP3, caspase-1 and GSDMD was up-regulated, and the expression of TIPE2 was down-regulated in group WT-ALI and group KO-ALI ( P<0.05). Compared with group WT-ALI, the lung injury score, W/D ratio, MPO activity and concentrations of IL-1β and IL-18 in serum were significantly increased, the expression of TREM-1, NLRP3, caspase-1 and GSDMD was up-regulated, and the expression of TIPE2 was down-regulated in group KO-ALI ( P<0.05). Conclusion:TIPE2 is involved in endogenous protective mechanism of ALI in septic mice, which is related to inhibition of activation of TREM-1/NLRP3 inflammasome signaling pathway.