Cardiopulmonary Bypass Down-Regulates NOD Signaling and Inflammatory Response in Children with Congenital Heart Disease.
In the present study, we aimed to examine the impact of cardiopulmonary bypass (CPB) on expression and function of NOD1 and NOD2 in children with congenital heart disease (CHD), in an attempt to clarify whether NOD1 and NOD2 signaling is involved in the modulation of host innate immunity against postoperative infection in pediatric CHD patients. Peripheral blood samples were collected from pediatric CHD patients at five different time points: before CPB, immediately after CPB, and 1, 3, and 7 days after CPB. Real-time PCR, Western blot, and ELISA were performed to measure the expression of NOD1 and NOD2, their downstream signaling pathways, and inflammatory cytokines at various time points. Proinflammatory cytokine IL-6 and TNF-α levels in response to stimulation with either the NOD1 agonist Tri-DAP or the NOD2 agonist MDP were significantly reduced after CPB compared with those before CPB, which is consistent with a suppressed inflammatory response postoperatively. The expression of phosphorylated RIP2 and activation of the downstream signaling pathways NF-κB p65 and MAPK p38 upon Tri-DAP or MDP stimulation in PBMCs were substantially inhibited after CPB. The mRNA level of NOD1 and protein levels of NOD1 and NOD2 were also markedly decreased after CPB. Our results demonstrated that NOD-mediated signaling pathways were substantially inhibited after CPB, which correlates with the suppressed inflammatory response and may account, at least in part, for the increased risk of postoperative infection in pediatric CHD patients.
Department of Pediatric Surgery, Children's Hospital of Soochow University, Suzhou, China.
Qinghua
Q
Yang
Department of Pediatric Surgery, Children's Hospital of Soochow University, Suzhou, China.
Jianyi
J
Liao
Department of Pediatric Cardiology, Children's Hospital of Soochow University, Suzhou, China.
Jie
J
Huang
Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, China.
Yi Ping
YP
Li
Department of Pediatric Surgery, Children's Hospital of Soochow University, Suzhou, China.
Shungen
S
Huang
Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, China.
Huiting
H
Zhou
Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, China.
Yi
Y
Xie
Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, China.
Jian
J
Pan
Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, China.
Yanhong
Y
Li
Department of Academic Surgery, University College Cork, Cork University Hospital, Cork, Ireland.
Jiang Huai
JH
Wang
Department of Pediatric Surgery, Children's Hospital of Soochow University, Suzhou, China.
Jian
J
Wang
D015153:Blotting, Western; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D015536:Down-Regulation / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006330:Heart Defects, Congenital / Q000378:metabolism / Q000601:surgery*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007223:Infant; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism / Q000502:physiology*; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015850:Interleukin-6; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D014409:Tumor Necrosis Factor-alpha