{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:50:44Z","timestamp":1792497044312,"version":"4.5.0"},"reference-count":95,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Intrauterine growth restriction (IUGR) is a relevant predictor for higher rates of neonatal sepsis worldwide and is associated with an impaired neonatal immunity and lower immune cell counts. During the perinatal period, the liver is a key immunological organ responsible for the nuclear factor kappa B (NF-\u03baB)-mediated innate immune response to inflammatory stimuli, but whether this role is affected by IUGR is unknown. Herein, we hypothesized that the newborn liver adapts to calorie-restriction IUGR by inducing changes in the NF-\u03baB signaling transcriptome, leading to an attenuated acute proinflammatory response to intraperitoneal lipopolysaccharide (LPS). We first assessed the hepatic gene expression of key NF-\u03baB factors in the IUGR and normally grown (NG) newborn mice. Real-time quantitative PCR (RT-qPCR) analysis revealed an upregulation of both I\u03baB proteins genes (<jats:italic>Nfkbia<\/jats:italic> and <jats:italic>Nfkbib<\/jats:italic>) and the NF-\u03baB subunit <jats:italic>Nfkb1<\/jats:italic> in IUGR <jats:italic>vs.<\/jats:italic> NG. We next measured the LPS-induced hepatic expression of acute proinflammatory genes (<jats:italic>Ccl3<\/jats:italic>, <jats:italic>Cxcl1<\/jats:italic>, <jats:italic>Il1b<\/jats:italic>, <jats:italic>Il6<\/jats:italic>, and <jats:italic>Tnf<\/jats:italic>) and observed that the IUGR liver produced an attenuated acute proinflammatory cytokine gene response (<jats:italic>Il1b and Tnf<\/jats:italic>) to LPS in IUGR <jats:italic>vs.<\/jats:italic> unexposed (CTR). Consistent with these results, LPS-exposed hepatic tumor necrosis factor alpha (TNF-\u03b1) protein concentrations were lower in IUGR <jats:italic>vs.<\/jats:italic> LPS-exposed NG and did not differ from IUGR CTR. Sex differences at the transcriptome level were observed in the IUGR male <jats:italic>vs.<\/jats:italic> female. Our results demonstrate that IUGR induces key modifications in the NF-\u03baB transcriptomic machinery in the newborn that compromised the acute proinflammatory cytokine gene and protein response to LPS. Our results bring novel insights in understanding how the IUGR newborn is immunocompromised due to fundamental changes in NF-\u03baB key factors.<\/jats:p>","DOI":"10.3389\/fimmu.2021.706774","type":"journal-article","created":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T01:45:36Z","timestamp":1630719936000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["The Acute Hepatic NF-\u03baB-Mediated Proinflammatory Response to Endotoxemia Is Attenuated in Intrauterine Growth-Restricted Newborn Mice"],"prefix":"10.3389","volume":"12","author":[{"given":"Miguel A.","family":"Zarate","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn K.","family":"De Dios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Durganili","family":"Balasubramaniyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura G.","family":"Sherlock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Rozance","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clyde J.","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00033.2015","article-title":"Intrauterine Growth Restriction: Hungry for an Answer","volume":"31","author":"Devaskar","year":"2016","journal-title":"Physiol (Bethesda)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/jp.2010.53","article-title":"Increased Cord Serum Inflammatory Markers in Small-for-Gestational-Age Neonates","volume":"31","author":"Amarilyo","year":"2011","journal-title":"J Perinatol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/s0002-9378(00)70513-8","article-title":"Morbidity and Mortality Among Very-Low-Birth-Weight Neonates With Intrauterine Growth Restriction. The Vermont Oxford Network","volume":"182","author":"Bernstein","year":"2000","journal-title":"Am J Obstet Gynecol"},{"key":"B4","article-title":"Intrauterine Growth Retardation (IUGR): Epidemiology and Etiology","author":"Romo","year":"2009","journal-title":"Pediatr Endocrinol Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-3782(14)70014-3","article-title":"IUGR and Infections","author":"Longo","year":"2014","journal-title":"Early Hum Dev"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1136\/adc.58.1.34","article-title":"Identification of Lymphocyte Subsets in the Newborn Using a Variety of Monoclonal Antibodies","volume":"58","author":"Thomas","year":"1983","journal-title":"Arch Dis Child"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1254547","article-title":"Intrauterine Growth Retardation in Preterm Infants <\/=32 Weeks of Gestation Is Associated With Low White Blood Cell Counts","volume":"27","author":"Wirbelauer","year":"2010","journal-title":"Am J Perinatol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/s0022-3476(78)80599-x","article-title":"Prolonged Impairment of Cellular Immunity in Children With Intrauterine Growth Retardation","volume":"93","author":"Ferguson","year":"1978","journal-title":"J Pediatr"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2014.02.055","article-title":"Intrauterine Growth Restriction and Prematurity Influence Regulatory T Cell Development in Newborns","volume":"49","author":"Mukhopadhyay","year":"2014","journal-title":"J Pediatr Surg"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/s0166-2236(96)01035-1","article-title":"NF-Kappa B: A Crucial Transcription Factor for Glial and Neuronal Cell Function","volume":"20","author":"O'Neill","year":"1997","journal-title":"Trends Neurosci"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21413","article-title":"NF-kB Induces Lung Maturation During Mouse Lung Morphogenesis","volume":"237","author":"Londhe","year":"2008","journal-title":"Dev Dyn"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2016.03.010","article-title":"The NF-kappaB Family: Key Players During Embryonic Development and HSC Emergence","volume":"44","author":"Espin-Palazon","year":"2016","journal-title":"Exp Hematol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2013.05.037","article-title":"NF-Kappab: Emerging Roles in Hippocampal Development and Function","volume":"45","author":"Crampton","year":"2013","journal-title":"Int J Biochem Cell Biol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/82_2010_103","article-title":"NF-kappaB and Mucosal Homeostasis","volume":"349","author":"Eckmann","year":"2011","journal-title":"Curr Top Microbiol Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.it.2014.04.007","article-title":"Ontogeny of Early Life Immunity","volume":"35","author":"Dowling","year":"2014","journal-title":"Trends Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.5.953","article-title":"NF-Kappa B RelA-Deficient Lymphocytes: Normal Development of T Cells and B Cells, Impaired Production of IgA and IgG1 and Reduced Proliferative Responses","volume":"185","author":"Doi","year":"1997","journal-title":"J Exp Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.21.11848","article-title":"The Combined Absence of the Transcription Factors Rel and RelA Leads to Multiple Hemopoietic Cell Defects","volume":"96","author":"Grossmann","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-009-9163-x","article-title":"Effects of Protein-Energy Malnutrition on NF-kappaB Signalling in Murine Peritoneal Macrophages","volume":"33","author":"Fock","year":"2010","journal-title":"Inflammation"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2015.08.001","article-title":"Control of Macrophage Metabolism and Activation by mTOR and Akt Signaling","volume":"27","author":"Covarrubias","year":"2015","journal-title":"Semin Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.11.7582","article-title":"Differential Involvement of IkappaB Kinases Alpha and Beta in Cytokine- and Insulin-Induced Mammalian Target of Rapamycin Activation Determined by Akt","volume":"180","author":"Dan","year":"2008","journal-title":"J Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2012.01095.x","article-title":"Regulation of Cell Death and Autophagy by IKK and NF-Kappab: Critical Mechanisms in Immune Function and Cancer","volume":"246","author":"Baldwin","year":"2012","journal-title":"Immunol Rev"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1080\/1745039X.2012.710084","article-title":"Effects of Intrauterine Growth Retardation and Maternal Folic Acid Supplementation on Hepatic Mitochondrial Function and Gene Expression in Piglets","volume":"66","author":"Liu","year":"2012","journal-title":"Arch Anim Nutr"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.6b00001","article-title":"Global Liver Proteome Analysis Using iTRAQ Reveals AMPK-mTOR-Autophagy Signaling Is Altered by Intrauterine Growth Restriction in Newborn Piglets","volume":"15","author":"Long","year":"2016","journal-title":"J Proteome Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2008.05.022","article-title":"Down-Regulation of Transcription Factor Peroxisome Proliferator-Activated Receptor in Programmed Hepatic Lipid Dysregulation and Inflammation in Intrauterine Growth-Restricted Offspring","volume":"199","author":"Magee","year":"2008","journal-title":"Am J Obstet Gynecol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2015.12.016","article-title":"Role of Placental Insufficiency and Intrauterine Growth Restriction on the Activation of Fetal Hepatic Glucose Production","volume":"435","author":"Wesolowski","year":"2016","journal-title":"Mol Cell Endocrinol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/978-94-009-3365-1_6","article-title":"Development of the Immune System in Human Fetal Liver","volume":"10","author":"Gale","year":"1987","journal-title":"Thymus"},{"key":"B27","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1002\/jlb.48.1.27","article-title":"Development, Differentiation, and Maturation of Macrophages in the Fetal Mouse Liver","volume":"48","author":"Naito","year":"1990","journal-title":"J Leukoc Biol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0029(19971115)39:4<350::AID-JEMT5>3.0.CO;2-L","article-title":"Development, Differentiation, and Maturation of Kupffer Cells","volume":"39","author":"Naito","year":"1997","journal-title":"Microsc Res Tech"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.11.6593","article-title":"The Fetal Liver Counterpart of Adult Common Lymphoid Progenitors Gives Rise to All Lymphoid Lineages, CD45+CD4+CD3- Cells, as Well as Macrophages","volume":"166","author":"Mebius","year":"2001","journal-title":"J Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2324","article-title":"NF-kappaB Controls Energy Homeostasis and Metabolic Adaptation by Upregulating Mitochondrial Respiration","volume":"13","author":"Mauro","year":"2011","journal-title":"Nat Cell Biol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/376167a0","article-title":"Embryonic Lethality and Liver Degeneration in Mice Lacking the RelA Component of NF-Kappa B","volume":"376","author":"Beg","year":"1995","journal-title":"Nature"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2011.13","article-title":"NF-kappaB in Immunobiology","volume":"21","author":"Hayden","year":"2011","journal-title":"Cell Res"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/s1074-7613(00)80451-3","article-title":"Failure of Lymphopoiesis After Adoptive Transfer of NF-kappaB-Deficient Fetal Liver Cells","volume":"6","author":"Horwitz","year":"1997","journal-title":"Immunity"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2010.213","article-title":"NF-kappaB in the Liver\u2013Linking Injury, Fibrosis and Hepatocellular Carcinoma","volume":"8","author":"Luedde","year":"2011","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501017","article-title":"Endotoxemia Induces IkappaBbeta\/NF-kappaB-Dependent Endothelin-1 Expression in Hepatic Macrophages","volume":"195","author":"McKenna","year":"2015","journal-title":"J Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1159\/000445541","article-title":"Perinatal Endotoxemia Induces Sustained Hepatic COX-2 Expression Through an NFkappaB-Dependent Mechanism","volume":"8","author":"McKenna","year":"2016","journal-title":"J Innate Immun"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02210","article-title":"Immunotolerant P50\/NFkappaB Signaling and Attenuated Hepatic IFNbeta Expression Increases Neonatal Sensitivity to Endotoxemia","volume":"9","author":"McKenna","year":"2018","journal-title":"Front Immunol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.3390\/nu10101531","article-title":"Immune Function and Micronutrient Requirements Change Over the Life Course","volume":"10","author":"Maggini","year":"2018","journal-title":"Nutrients"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00034.2013","article-title":"Intrauterine Calorie Restriction Affects Placental DNA Methylation and Gene Expression","volume":"45","author":"Chen","year":"2013","journal-title":"Physiol Genomics"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24568","article-title":"Murine Maternal Dietary Restriction Affects Neural Humanin Expression and Cellular Profile","volume":"98","author":"Baldauf","year":"2020","journal-title":"J\u00a0Neurosci Res"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1210\/en.2016-1259","article-title":"Maternal Calorie Restriction Causing Uteroplacental Insufficiency Differentially Affects Mammalian Placental Glucose and Leucine Transport Molecular Mechanisms","volume":"157","author":"Ganguly","year":"2016","journal-title":"Endocrinology"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.nutres.2016.08.001","article-title":"Gestational Food Restriction Decreases Placental Interleukin-10 Expression and Markers of Autophagy and Endoplasmic Reticulum Stress in Murine Intrauterine Growth Restriction","volume":"36","author":"Chu","year":"2016","journal-title":"Nutr Res"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01555","article-title":"Developmentally Regulated Innate Immune NFkappaB Signaling Mediates IL-1alpha Expression in the Perinatal Murine Lung","volume":"10","author":"Butler","year":"2019","journal-title":"Front Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1177\/1753425918823900","article-title":"The Hepatic Innate Immune Response Is Lobe-Specific in a Murine Model Endotoxemia","volume":"25","author":"Nguyen","year":"2019","journal-title":"Innate Immun"},{"key":"B45","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen Recognition and Innate Immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.621","article-title":"Phosphorylation Meets Ubiquitination: The Control of NF-[Kappa]B Activity","volume":"18","author":"Karin","year":"2000","journal-title":"Annu Rev Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2008.01.006","article-title":"LPS\/TLR4 Signal Transduction Pathway","volume":"42","author":"Lu","year":"2008","journal-title":"Cytokine"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1606","article-title":"Sequential Control of Toll-Like Receptor-Dependent Responses by IRAK1 and IRAK2","volume":"9","author":"Kawagoe","year":"2008","journal-title":"Nat Immunol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/nri1391","article-title":"Toll-Like Receptor Signalling","volume":"4","author":"Akira","year":"2004","journal-title":"Nat Rev Immunol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3390\/cells5010012","article-title":"The Regulation of NF-kappaB Subunits by Phosphorylation","volume":"5","author":"Christian","year":"2016","journal-title":"Cells"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2009.111","article-title":"Mechanisms of Liver Disease: Cross-Talk Between the NF-kappaB and JNK Pathways","volume":"390","author":"Papa","year":"2009","journal-title":"Biol Chem"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.16.1.225","article-title":"NF-Kappa B and Rel Proteins: Evolutionarily Conserved Mediators of Immune Responses","volume":"16","author":"Ghosh","year":"1998","journal-title":"Annu Rev Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1203\/01.pdr.0000196332.37565.7d","article-title":"Cytokines in the Placenta of Pakistani Newborns With and Without Intrauterine Growth Retardation","volume":"59","author":"Amu","year":"2006","journal-title":"Pediatr Res"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1093\/tropej\/43.6.345","article-title":"Immune Status of Full-Term Small-for-Gestational Age Neonates in India","volume":"43","author":"Chatrath","year":"1997","journal-title":"J Trop Pediatr"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e31821f6e75","article-title":"Intrauterine Growth Restriction Alters T-Lymphocyte Cell Number and Dual Specificity Phosphatase 1 Levels in the Thymus of Newborn and Juvenile Rats","volume":"70","author":"Contreras","year":"2011","journal-title":"Pediatr Res"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02402","article-title":"Growth Restriction and Systemic Immune Development in Preterm Piglets","volume":"10","author":"Baek","year":"2019","journal-title":"Front Immunol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a000034","article-title":"The NF-kappaB Family of Transcription Factors and Its Regulation","volume":"1","author":"Oeckinghaus","year":"2009","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.16.5.2341","article-title":"IkappaBalpha Deficiency Results in a Sustained NF-kappaB Response and Severe Widespread Dermatitis in Mice","volume":"16","author":"Klement","year":"1996","journal-title":"Mol Cell Biol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.02.009","article-title":"Stroma-Mediated Dysregulation of Myelopoiesis in Mice Lacking I Kappa B Alpha","volume":"22","author":"Rupec","year":"2005","journal-title":"Immunity"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1038\/nature09283","article-title":"IkappaBbeta Acts to Inhibit and Activate Gene Expression During the Inflammatory Response","volume":"466","author":"Rao","year":"2010","journal-title":"Nature"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5234.286","article-title":"Immunosuppression by Glucocorticoids: Inhibition of NF-Kappa B Activity Through Induction of I Kappa B Synthesis","volume":"270","author":"Auphan","year":"1995","journal-title":"Science"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.23.14214","article-title":"Induction and Stabilization of I Kappa B Alpha by Nitric Oxide Mediates Inhibition of NF-Kappa B","volume":"270","author":"Peng","year":"1995","journal-title":"J Biol Chem"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.11.027","article-title":"Inflammation and Postinfarct Remodeling: Overexpression of IkappaB Prevents Ventricular Dilation via Increasing TIMP Levels","volume":"69","author":"Trescher","year":"2006","journal-title":"Cardiovasc Res"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.043034","article-title":"Nuclear Factor {Kappa}B Inactivation in the Rat Liver Ameliorates Short Term Total Warm Ischaemia\/Reperfusion Injury","volume":"54","author":"Suetsugu","year":"2005","journal-title":"Gut"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032811","article-title":"Nfkb1 Inhibits LPS-Induced IFN-Beta and IL-12 P40 Production in Macrophages by Distinct Mechanisms","volume":"7","author":"Zhao","year":"2012","journal-title":"PLoS One"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809784106","article-title":"Tolerance and M2 (Alternative) Macrophage Polarization Are Related Processes Orchestrated by P50 Nuclear Factor kappaB","volume":"106","author":"Porta","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2004.03.008","article-title":"The Two NF-kappaB Activation Pathways and Their Role in Innate and Adaptive Immunity","volume":"25","author":"Bonizzi","year":"2004","journal-title":"Trends Immunol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1038\/nri910","article-title":"NF-kappaB Regulation in the Immune System","volume":"2","author":"Li","year":"2002","journal-title":"Nat Rev Immunol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2011.04.051","article-title":"Macrophage Genetic Reprogramming During Chronic Peritonitis Is Augmented by LPS Pretreatment","volume":"175","author":"Kanaan","year":"2012","journal-title":"J Surg Res"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021891","article-title":"Gastrodin Inhibits Expression of Inducible NO Synthase, Cyclooxygenase-2 and Proinflammatory Cytokines in Cultured LPS-Stimulated Microglia via MAPK Pathways","volume":"6","author":"Dai","year":"2011","journal-title":"PLoS One"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2006.05.023","article-title":"The Alabama Preterm Birth Study: Intrauterine Infection and Placental Histologic Findings in Preterm Births of Males and Females Less Than 32 Weeks","volume":"195","author":"Goldenberg","year":"2006","journal-title":"Am J Obstet Gynecol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-018-0713-x","article-title":"Developmental Origin and Sex-Specific Risk for Infections and Immune Diseases Later in Life","volume":"41","author":"Zazara","year":"2019","journal-title":"Semin Immunopathol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmi008","article-title":"Sex Hormones and the Immune Response in Humans","volume":"11","author":"Bouman","year":"2005","journal-title":"Hum Reprod Update"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1038\/nri2394","article-title":"The X-Files in Immunity: Sex-Based Differences Predispose Immune Responses","volume":"8","author":"Fish","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"B75","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s11689-019-9297-6","article-title":"Reducing Th2 Inflammation Through Neutralizing IL-4 Antibody Rescues Myelination in IUGR Rat Brain","volume":"11","author":"Zanno","year":"2019","journal-title":"J Neurodev Disord"},{"key":"B76","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s12974-018-1392-1","article-title":"Neuropathology in Intrauterine Growth Restricted Newborn Piglets Is Associated With Glial Activation and Proinflammatory Status in the Brain","volume":"16","author":"Wixey","year":"2019","journal-title":"J\u00a0Neuroinflamm"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1177\/1933719110364061","article-title":"Brain Injury Caused by Chronic Fetal Hypoxemia Is Mediated by Inflammatory Cascade Activation","volume":"17","author":"Guo","year":"2010","journal-title":"Reprod Sci"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2012.26","article-title":"Intracerebral Lipopolysaccharide Induces Neuroinflammatory Change and Augmented Brain Injury in Growth-Restricted Neonatal Rats","volume":"71","author":"Campbell","year":"2012","journal-title":"Pediatr Res"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1334879","article-title":"Levels of Cytokines in Umbilical Cord Blood in Small for Gestational Age Preterm Infants","volume":"225","author":"Lindner","year":"2013","journal-title":"Klin Padiatr"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwq028","article-title":"Umbilical Cord Serum Cytokine Levels and Risks of Small-for-Gestational-Age and Preterm Birth","volume":"171","author":"Neta","year":"2010","journal-title":"Am J Epidemiol"},{"key":"B81","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1159\/000343260","article-title":"Intrauterine Growth Restriction and the Innate Immune System in Preterm Infants of <\/=32 Weeks Gestation","volume":"103","author":"Troger","year":"2013","journal-title":"Neonatology"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.3109\/15513815.2013.879239","article-title":"Inflammatory Markers in Umbilical Cord Blood From Small-for-Gestational-Age Newborns","volume":"33","author":"Lausten-Thomsen","year":"2014","journal-title":"Fetal Pediatr Pathol"},{"key":"B83","doi-asserted-by":"publisher","first-page":"51","DOI":"10.3233\/DMA-2012-0903","article-title":"Cord Blood Levels of IL-6, IL-8 and IL-10 May Be Early Predictors of Bronchopulmonary Dysplasia in Preterm Newborns Small for Gestational Age","volume":"33","author":"Rocha","year":"2012","journal-title":"Dis Markers"},{"key":"B84","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1007\/s12192-012-0326-6","article-title":"Impairment of Cellular Immunity Is Associated With Overexpression of Heat Shock Protein 70 in Neonatal Pigs With Intrauterine Growth Retardation","volume":"17","author":"Zhong","year":"2012","journal-title":"Cell Stress Chaperones"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-019-01867-w","article-title":"Intrauterine Growth Restriction Induces Skin Inflammation, Increases TSLP and Impairs Epidermal Barrier Function","volume":"98","author":"Polanyi","year":"2020","journal-title":"J Mol Med (Berl)"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2013.03.001","article-title":"Maternal Magnesium Supplementation Reduces Intrauterine Growth Restriction and Suppresses Inflammation in a Rat Model","volume":"208","author":"Roman","year":"2013","journal-title":"Am J Obstet Gynecol"},{"key":"B87","doi-asserted-by":"crossref","DOI":"10.1007\/s13669-013-0041-z","article-title":"Intrauterine Growth Restriction (IUGR): Etiology and Diagnosis","volume":"2","author":"Suhag","year":"2013","journal-title":"Curr Obstet Gynecol Rep"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2017.04.013","article-title":"Hypoxia Augments LPS-Induced Inflammation and Triggers High Altitude Cerebral Edema in Mice","volume":"64","author":"Zhou","year":"2017","journal-title":"Brain Behav Immun"},{"key":"B89","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s12950-018-0197-4","article-title":"The Severity of LPS Induced Inflammatory Injury Is Negatively Associated With the Functional Liver Mass After LPS Injection in Rat Model","volume":"15","author":"Fang","year":"2018","journal-title":"J Inflamm (Lond)"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.1997.5062","article-title":"Starvation Enhances Hepatic Free Radical Release Following Endotoxemia","volume":"69","author":"Robinson","year":"1997","journal-title":"J Surg Res"},{"key":"B91","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1007\/s00726-021-02940-w","article-title":"Effects of Different Branched-Chain Amino Acids Supplementation Protocols on the Inflammatory Response of LPS-Stimulated RAW 264.7 Macrophages","volume":"53","author":"Bonvini","year":"2021","journal-title":"Amino Acids"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1097\/00005176-198803000-00012","article-title":"Endotoxemia in Protein-Energy Malnutrition","volume":"7","author":"Klein","year":"1988","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2006.00072.x","article-title":"Oxidative Stress and Septic Shock: Metabolic Aspects of Oxygen-Derived Free Radicals Generated in the Liver During Endotoxemia","volume":"47","author":"Sakaguchi","year":"2006","journal-title":"FEMS Immunol Med Microbiol"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.2527\/jas.2013-6824","article-title":"Intrauterine Growth Restricted Piglets Defined by Their Head Shape Ingest Insufficient Amounts of Colostrum","volume":"91","author":"Amdi","year":"2013","journal-title":"J Anim Sci"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064616","article-title":"Postnatal Leptin Promotes Organ Maturation and Development in IUGR Piglets","volume":"8","author":"Attig","year":"2013","journal-title":"PLoS One"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.706774\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T01:45:42Z","timestamp":1630719942000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.706774\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,1]]},"references-count":95,"alternative-id":["10.3389\/fimmu.2021.706774"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.706774","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,1]]},"article-number":"706774"}}