Cardiopulmonary bypass down-regulates NOD signaling and inflammatory response in children with congenital heart disease

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dc.contributor.authorYang, Qinghua
dc.contributor.authorLiao, Jianyi
dc.contributor.authorHuang, Jie
dc.contributor.authorLi, Yi Ping
dc.contributor.authorHuang, Shungen
dc.contributor.authorZhou, Huiting
dc.contributor.authorXie, Yi
dc.contributor.authorPan, Jian
dc.contributor.authorLi, Yanhong
dc.contributor.authorWang, Jiang Huai
dc.contributor.authorWang, Jian
dc.contributor.funderNational Natural Science Foundation of China
dc.contributor.funderNational Natural Science Foundation of Jiangsu Province, China
dc.contributor.funderInnovative Team of Jiangsu Province, China
dc.contributor.funderJiangsu Province Program of Innovative and Entrepreneurial Talents, China
dc.date.accessioned2016-10-10T11:12:20Z
dc.date.available2016-10-10T11:12:20Z
dc.date.issued2016-09-13
dc.description.abstractIn 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. Proinflammatorycytokine 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.en
dc.description.sponsorshipNational Natural Science Foundation of China (Grants 81272143 and 81420108022); National Natural Science Foundation of Jiangsu Province, China (Grant BK2011310); Innovative Team of Jiangsu Province, China (Grant LJ201141), and Jiangsu Province Program of Innovative and Entrepreneurial Talents, China (2011-2014)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleide0162179
dc.identifier.citationYang, Q., Liao, J., Huang, J., Li, Y.P., Huang, S., Zhou, H., Xie, Y., Pan, J., Li, Y., Wang, J.H. and Wang, J. (2016) 'Cardiopulmonary bypass down-regulates NOD signaling and inflammatory response in children with congenital heart disease', PLoS ONE, 11(9), e0162179 (11pp). doi:10.1371/journal.pone.0162179en
dc.identifier.doi10.1371/journal.pone.0162179
dc.identifier.endpage11en
dc.identifier.issn1932-6203
dc.identifier.issued9en
dc.identifier.journaltitlePLoS ONEen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/3171
dc.identifier.volume11en
dc.language.isoenen
dc.publisherPublic Library of Scienceen
dc.rights© 2016 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectCongenital heart diseaseen
dc.subjectNOD1en
dc.subjectNOD2en
dc.subjectImmunityen
dc.subjectPostoperative infectionen
dc.titleCardiopulmonary bypass down-regulates NOD signaling and inflammatory response in children with congenital heart diseaseen
dc.typeArticle (peer-reviewed)en
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