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.
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.
ABSTRACT
Liver and gastrointestinal tumors greatly threaten human health and have poor therapeutic outcomes and prognosis.Tumor necrosis factor -alpha -induced protein 8 -like 2 (TIPE2)can negatively regulate innate immunity and adaptive immunity and maintain immune ho-meostasis.Recent studies have found that TIPE2 can affect various signaling pathways and thus exerts an inhibitory effect on the development and progression of tumors.This article briefly introduces the structure and function of TIPE2 and its regulatory effect on tumor -related sig-naling pathways such as Ras,Ral,and Rac and downstream molecules,as well as the role of TIPE2 in liver and gastrointestinal tumors,re-lated signaling pathways,and research advances.