RGD Reference Report - Deficiency of Interleukin-36 Receptor Protected Cardiomyocytes from Ischemia-Reperfusion Injury in Cardiopulmonary Bypass. - Rat Genome Database

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Deficiency of Interleukin-36 Receptor Protected Cardiomyocytes from Ischemia-Reperfusion Injury in Cardiopulmonary Bypass.

Authors: Luo, Cheng  Xie, Xiaoyong  Feng, Xu  Lei, Binfeng  Fang, Chen  Li, Yugui  Cai, Xiongwei  Ling, Guoxing  Zheng, Baoshi 
Citation: Luo C, etal., Med Sci Monit. 2020 Feb 12;26:e918933. doi: 10.12659/MSM.918933.
RGD ID: 126925167
Pubmed: PMID:32048631   (View Abstract at PubMed)
PMCID: PMC7034403   (View Article at PubMed Central)
DOI: DOI:10.12659/MSM.918933   (Journal Full-text)

BACKGROUND Interleukin-36 has been demonstrated to be involved in inflammatory responses. Inflammatory responses due to ischemia-reperfusion injury following cardiopulmonary bypass (CPB) can cause heart dysfunction or damage. MATERIAL AND METHODS The CPB models were constructed in IL-36R-/-, IL-36RN-/-, and wild-type SD rats. Ultrasonic cardiography and ELISA were used to evaluate the cardiac function and measuring myocardial biomarker levels in different groups. TUNEL assay was used to evaluate apoptosis. Western blot assays and RT-PCR were performed to measure the expression of chemokines and secondary inflammatory cytokines in the heart. Oxidative stress in tissue and cultured cells was assessed using a DCFH-DA fluorescence probe and quantification of superoxide dismutase activity. RESULTS Improved systolic function and decreased serum levels of myocardial damage biomarkers were found in IL-36R-/- rats compared to WT rats, while worse cardiac function and cardiomyocyte IR injury were observed in IL-36RN-/- rats compared to WT rats. TUNEL staining and Western blot analyses found that cardiomyocyte apoptosis and inflammation were significantly lower in the hearts of IL-36R-/- rats compared with that of WT rats. Oxidative stress was significantly lower in IL-36R-/- rats compared to WT rats. iNOS expression was significantly reduced, while eNOS expression was increased in the hearts of IL-36R-/- rats. Silencing of IL-36R expression in vitro activated SIRT1/FOXO1/p53 signaling in cardiomyocytes. CONCLUSIONS IL-36R deficiency in cardiomyocytes repressed infiltration of bone marrow-derived inflammatory cells and oxidative stress dependent on SIRT1-FOXO1 signaling, thus protecting cardiomyocytes and improving cardiac function in CPB model rats.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL1RL2HumanMyocardial Reperfusion Injury  ISORGD:621782compared to Wild Type in cardiopulmonary bypass modelRGD 
IL36RNHumanMyocardial Reperfusion Injury  ISORGD:1311212 RGD 
Il1rl2RatMyocardial Reperfusion Injury  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2MouseMyocardial Reperfusion Injury  ISORGD:621782compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2tm1(Myh6-cre)MhzhRatMyocardial Reperfusion Injury  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il36rnRatMyocardial Reperfusion Injury  IMP  RGD 
Il36rnMouseMyocardial Reperfusion Injury  ISORGD:1311212 RGD 
Il36rntm1(Myh6-cre)MhzhRatMyocardial Reperfusion Injury  IMP  RGD 
SD-Il1rl2tm1(Myh6-cre)MhzhRatMyocardial Reperfusion Injury  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
SD-Il36rntm1(Myh6-cre)MhzhRatMyocardial Reperfusion Injury  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Il1rl2Ratabnormal circulating chemokine level  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2tm1(Myh6-cre)MhzhRatabnormal circulating chemokine level  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
SD-Il1rl2tm1(Myh6-cre)MhzhRatabnormal circulating chemokine level  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2Ratabnormal circulating myoglobin level  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2tm1(Myh6-cre)MhzhRatabnormal circulating myoglobin level  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
SD-Il1rl2tm1(Myh6-cre)MhzhRatabnormal circulating myoglobin level  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2Ratabnormal nitric oxide homeostasis  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2tm1(Myh6-cre)MhzhRatabnormal nitric oxide homeostasis  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
SD-Il1rl2tm1(Myh6-cre)MhzhRatabnormal nitric oxide homeostasis  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2Ratdecreased cardiomyocyte apoptosis  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2tm1(Myh6-cre)MhzhRatdecreased cardiomyocyte apoptosis  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
SD-Il1rl2tm1(Myh6-cre)MhzhRatdecreased cardiomyocyte apoptosis  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2Ratdecreased circulating lactate dehydrogenase level  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2tm1(Myh6-cre)MhzhRatdecreased circulating lactate dehydrogenase level  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
SD-Il1rl2tm1(Myh6-cre)MhzhRatdecreased circulating lactate dehydrogenase level  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2Ratdecreased circulating troponin level  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2tm1(Myh6-cre)MhzhRatdecreased circulating troponin level  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
SD-Il1rl2tm1(Myh6-cre)MhzhRatdecreased circulating troponin level  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2Ratdecreased circulating tumor necrosis factor level  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2tm1(Myh6-cre)MhzhRatdecreased circulating tumor necrosis factor level  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
SD-Il1rl2tm1(Myh6-cre)MhzhRatdecreased circulating tumor necrosis factor level  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il36rnRatdecreased heart ventricle muscle contractility  IMP  RGD 
Il36rntm1(Myh6-cre)MhzhRatdecreased heart ventricle muscle contractility  IMP  RGD 
SD-Il36rntm1(Myh6-cre)MhzhRatdecreased heart ventricle muscle contractility  IMP  RGD 
Il1rl2Ratdecreased interleukin-1 beta secretion  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2tm1(Myh6-cre)MhzhRatdecreased interleukin-1 beta secretion  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
SD-Il1rl2tm1(Myh6-cre)MhzhRatdecreased interleukin-1 beta secretion  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il36rnRatdecreased left ventricle systolic pressure  IMP  RGD 
Il36rntm1(Myh6-cre)MhzhRatdecreased left ventricle systolic pressure  IMP  RGD 
SD-Il36rntm1(Myh6-cre)MhzhRatdecreased left ventricle systolic pressure  IMP  RGD 
Il1rl2Ratdecreased macrophage cell number  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2tm1(Myh6-cre)MhzhRatdecreased macrophage cell number  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
SD-Il1rl2tm1(Myh6-cre)MhzhRatdecreased macrophage cell number  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2Ratincreased cardiac muscle contractility  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2tm1(Myh6-cre)MhzhRatincreased cardiac muscle contractility  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
SD-Il1rl2tm1(Myh6-cre)MhzhRatincreased cardiac muscle contractility  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il36rnRatincreased circulating lactate dehydrogenase level  IMP  RGD 
Il36rntm1(Myh6-cre)MhzhRatincreased circulating lactate dehydrogenase level  IMP  RGD 
SD-Il36rntm1(Myh6-cre)MhzhRatincreased circulating lactate dehydrogenase level  IMP  RGD 
Il36rnRatincreased circulating myoglobin level  IMP  RGD 
Il36rntm1(Myh6-cre)MhzhRatincreased circulating myoglobin level  IMP  RGD 
SD-Il36rntm1(Myh6-cre)MhzhRatincreased circulating myoglobin level  IMP  RGD 
Il36rnRatincreased circulating troponin level  IMP  RGD 
Il36rntm1(Myh6-cre)MhzhRatincreased circulating troponin level  IMP  RGD 
SD-Il36rntm1(Myh6-cre)MhzhRatincreased circulating troponin level  IMP  RGD 
Il1rl2Ratincreased left ventricle systolic pressure  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2tm1(Myh6-cre)MhzhRatincreased left ventricle systolic pressure  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
SD-Il1rl2tm1(Myh6-cre)MhzhRatincreased left ventricle systolic pressure  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2Ratoxidative stress  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Il1rl2tm1(Myh6-cre)MhzhRatoxidative stress  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
SD-Il1rl2tm1(Myh6-cre)MhzhRatoxidative stress  IMP compared to Wild Type in cardiopulmonary bypass modelRGD 
Objects Annotated

Genes (Rattus norvegicus)
Il1rl2  (interleukin 1 receptor-like 2)
Il1rl2tm1(Myh6-cre)Mhzh  (interleukin 1 receptor-like 2; tm1 (Myh6-cre), Mhzh)
Il36rn  (interleukin 36 receptor antagonist)
Il36rntm1(Myh6-cre)Mhzh  (interleukin 36 receptor antagonist; tm1, Mhzh)

Genes (Mus musculus)
Il1rl2  (interleukin 1 receptor-like 2)
Il36rn  (interleukin 36 receptor antagonist)

Genes (Homo sapiens)
IL1RL2  (interleukin 1 receptor like 2)
IL36RN  (interleukin 36 receptor antagonist)


Additional Information