|Pretreatment with interleukin-33 reduces warm hepatic ischemia/reperfusion injury in mice|
|Li Shu; Zhu Feng-xue; Zhang Hong-bin; Li Hui; An You-zhong|
|关键词||liver ischemia/reperfusion T helper lymphocyte interleukin-33|
|刊名||CHINESE MEDICAL JOURNAL|
|WOS标题词||Science & Technology|
|类目[WOS]||Medicine, General & Internal|
|研究领域[WOS]||General & Internal Medicine|
|关键词[WOS]||REPERFUSION INJURY ; NKT CELLS ; LIVER ; IL-33 ; HEPATOCYTES ; ISCHEMIA ; PROTECTS ; RECEPTOR ; INNATE ; MOUSE|
Background Interleukin (IL)-33 is a recently identified member of the IL-1 family that binds to the receptor, ST2L. This study examined IL-33 production in mouse liver and investigated its role in hepatic ischemia/reperfusion (I/R) injury.
Methods Male BALB/c mice ((22 +/- 3) g) were subjected to 90 minutes partial hepatic ischemia, followed by 6 hours reperfusion. First, mice were randomized into two groups: control group (laparotomy only, without blocking blood supply) and ischennia model group. IL-33 mRNA and serum protein levels were measured at 30, 60, 90 minutes after ischemia and 2 and 6 hours after reperfusion. Second, mice were randomized into four groups: control, model (injection of rabbit IgG polyclonal antibody), recombinant IL-33 intervention and anti-ST2L antibody intervention group. Mice were sacrificed 6 hours after reperfusion. Liver pathology was observed via transmission electron microscopy. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), IL-4, IL-5, IL-13, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) levels were measured.
Results Levels of IL-33 mRNA and protein did not change during ischemia (P > 0.05) but increased significantly during reperfusion (P < 0.05). After reperfusion for 6 hours, serum levels of ALT, AST, IL-4, IL-5, IL-13, IFN-gamma and TNF-alpha were significantly increased (P < 0.05), and hepatocellular ultrastructure was damaged. Pretreatment with IL-33 attenuated severity of liver damage compared with controls, but pretreatment with anti-ST2L antibody increased severity. Serum levels of IL-4, IL-5 and IL-13 protein increased whereas IFN-gamma decreased following IL-33 pretreatment. Pretreatment with anti-ST2L antibody significantly decreased serum IL-4, IL-5, IL-13 levels and increased serum IFN-gamma levels compared with controls (P < 0.05). There was no change in the level of TNF-alpha.
Conclusion IL-33 is produced systematically and locally in liver during I/R injury. Pretreatment with IL-33 is therapeutic for hepatic I/R injury, possibly via inducing a Th1 to Th2 shift.
|资助机构||Peking University People&prime ; s Hospital Research and Development Funds|
|作者单位||Peking Univ, Peoples Hosp, Dept Crit Care Med, Beijing 100044, Peoples R China|
|Li Shu,Zhu Feng-xue,Zhang Hong-bin,et al. Pretreatment with interleukin-33 reduces warm hepatic ischemia/reperfusion injury in mice[J]. CHINESE MEDICAL JOURNAL,2013,126(10):1855-1859.|
|APA||Li Shu,Zhu Feng-xue,Zhang Hong-bin,Li Hui,&An You-zhong.(2013).Pretreatment with interleukin-33 reduces warm hepatic ischemia/reperfusion injury in mice.CHINESE MEDICAL JOURNAL,126(10),1855-1859.|
|MLA||Li Shu,et al."Pretreatment with interleukin-33 reduces warm hepatic ischemia/reperfusion injury in mice".CHINESE MEDICAL JOURNAL 126.10(2013):1855-1859.|