Altered inflammasome activation in neonatal encephalopathy persists in childhood

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dc.contributor.authorKelly, Lynne A.
dc.contributor.authorO'Dea, Mary I.
dc.contributor.authorZareen, Zunera
dc.contributor.authorMelo, A. M.
dc.contributor.authorMcKenna, Ellen
dc.contributor.authorStrickland, Tammy
dc.contributor.authorMcEneaney, V.
dc.contributor.authorDonoghue, Veronica
dc.contributor.authorBoylan, Geraldine B.
dc.contributor.authorSweetman, Deirdre
dc.contributor.authorButler, J.
dc.contributor.authorVavasseur, Claudine
dc.contributor.authorMiletin, Jan
dc.contributor.authorEl-Khuffash, Afif
dc.contributor.authorO'Neill, Luke
dc.contributor.authorO'Leary, John
dc.contributor.authorMolloy, Eleanor J.
dc.contributor.funderNational Children's Research Centreen
dc.contributor.funderHealth Research Boarden
dc.date.accessioned2022-04-26T11:10:48Z
dc.date.available2022-04-26T11:10:48Z
dc.date.issued2021-07
dc.date.updated2022-04-26T10:31:26Z
dc.description.abstractNeonatal encephalopathy (NE) is characterized by altered neurological function in term infants and inflammation plays an important pathophysiological role. Inflammatory cytokines interleukin (IL)-1 beta, IL-1ra and IL-18 are activated by the nucleotide-binding and oligomerization domain (NOD)-, leucine-rich repeat domain (LRR)- and NOD-like receptor protein 3 (NLRP3) inflammasome; furthermore, we aimed to examine the role of the inflammasome multiprotein complex involved in proinflammatory responses from the newborn period to childhood in NE. Cytokine concentrations were measured by multiplex enzyme-linked immunosorbent assay (ELISA) in neonates and children with NE in the absence or presence of lipopolysaccharide (LPS) endotoxin. We then investigated expression of the NLRP3 inflammasome genes, NLRP3, IL-1 beta and ASC by polymerase chain reaction (PCR). Serum samples from 40 NE patients at days 1 and 3 of the first week of life and in 37 patients at age 4-7 years were analysed. An increase in serum IL-1ra and IL-18 in neonates with NE on days 1 and 3 was observed compared to neonatal controls. IL-1ra in NE was decreased to normal levels at school age, whereas serum IL-18 in NE was even higher at school age compared to school age controls and NE in the first week of life. Percentage of LPS response was higher in newborns compared to school-age NE. NLRP3 and IL-1 beta gene expression were up-regulated in the presence of LPS in NE neonates and NLRP3 gene expression remained up-regulated at school age in NE patients compared to controls. Increased inflammasome activation in the first day of life in NE persists in childhood, and may increase the window for therapeutic intervention.en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationKelly, L. A., O'Dea, M. I., Zareen, Z., Melo, A. M., McKenna, E., Strickland, T., McEneaney, V., Donoghue, V., Boylan, G. B., Sweetman, D., Butler, J., Vavasseur, C., Miletin, J., El-Khuffash, A. F., O'Neill, L. A. J., O'Leary, J. J. and Molloy, E. J. (2021) 'Altered inflammasome activation in neonatal encephalopathy persists in childhood', Clinical and Experimental Immunology, 205 (1), pp. 89-97. doi: 10.1111/cei.13598en
dc.identifier.doi10.1111/cei.13598en
dc.identifier.endpage97en
dc.identifier.issn0009-9104
dc.identifier.issued1en
dc.identifier.journaltitleClinical and Experimental Immunologyen
dc.identifier.startpage89en
dc.identifier.urihttps://hdl.handle.net/10468/13117
dc.identifier.volume205en
dc.language.isoenen
dc.publisherJohn Wiley and Sons Ltden
dc.rights© 2021 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology., Clinical and Experimental Immunology, 205: 89–97. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectNLRP3 inflammasomeen
dc.subjectInterleukin-1en
dc.subjectHypothermiaen
dc.subjectCytokinesen
dc.subjectTermen
dc.subjectResponsesen
dc.subjectMatteren
dc.subjectModelen
dc.subjectTrialen
dc.subjectSchemic brain-injuryen
dc.titleAltered inflammasome activation in neonatal encephalopathy persists in childhooden
dc.typeArticle (peer-reviewed)en
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