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Tytuł:
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Intrauterine growth restriction leads to a high-corticosterone producing offspring: An implication for pulmonary infection susceptibility.
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Autorzy:
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Gil NL; Department of Pharmaceuticals Sciences, Universidade Federal de São Paulo-campus Diadema, Diadema, SP, Brazil.
Azevedo GA; Department of Pharmaceuticals Sciences, Universidade Federal de São Paulo-campus Diadema, Diadema, SP, Brazil.
Balbino AM; Department of Pharmaceuticals Sciences, Universidade Federal de São Paulo-campus Diadema, Diadema, SP, Brazil.
Silva MM; Department of Pharmaceuticals Sciences, Universidade Federal de São Paulo-campus Diadema, Diadema, SP, Brazil.
Carvalho MHC; Department of Pharmacology, Universidade de São Paulo, São Paulo, SP, Brazil.
Akamine EH; Department of Pharmacology, Universidade de São Paulo, São Paulo, SP, Brazil.
Keller AC; Department of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Landgraf RG; Department of Pharmaceuticals Sciences, Universidade Federal de São Paulo-campus Diadema, Diadema, SP, Brazil. Electronic address: .
Landgraf MA; Universidade Paulista - campus Rangel, Santos, SP, Brazil. Electronic address: .
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Źródło:
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Life sciences [Life Sci] 2021 Sep 15; Vol. 281, pp. 119764. Date of Electronic Publication: 2021 Jun 26.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: <2008->: Amsterdam : Elsevier
Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press.
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MeSH Terms:
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Disease Susceptibility*
Fetal Growth Retardation*
Prenatal Exposure Delayed Effects*
Corticosterone/*biosynthesis
Pneumonia, Bacterial/*immunology
Animals ; Arachidonic Acid/metabolism ; Female ; Hypothalamo-Hypophyseal System/metabolism ; Lipopolysaccharides/administration & dosage ; Lung/drug effects ; Lung/metabolism ; Male ; NF-kappa B/metabolism ; Pituitary-Adrenal System/metabolism ; Pregnancy ; Rats ; Rats, Wistar ; Toll-Like Receptor 4/metabolism
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Contributed Indexing:
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Keywords: Acute lung inflammation; Foetal programming; Intrauterine growth restriction; Low birth weight; Maternal undernutrition
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Substance Nomenclature:
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0 (Lipopolysaccharides)
0 (NF-kappa B)
0 (Tlr4 protein, rat)
0 (Toll-Like Receptor 4)
27YG812J1I (Arachidonic Acid)
W980KJ009P (Corticosterone)
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Entry Date(s):
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Date Created: 20210629 Date Completed: 20210810 Latest Revision: 20210810
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Update Code:
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20240105
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DOI:
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10.1016/j.lfs.2021.119764
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PMID:
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34186045
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Aims: Although intrauterine growth restriction (IUGR) impairs immune system homeostasis and lung development, its relationship with the susceptibility to pulmonary infections remains unclear. Thus, this study aimed to investigate the impact of IUGR on acute lung inflammatory response induced by bacterial stimulus.
Materials and Methods: Pregnant female Wistar rats were subjected to 50% caloric-protein food restriction during gestation. To mimic bacterial lung infection, adult male offspring (12 weeks old) were challenged with a single lipopolysaccharide (LPS) intranasal instillation, and 6 h later, we assessed the acute inflammatory response. Normal birth weight (NBW) animals represent the control group.
Key Findings: LPS instillation increased the protein levels in the airways of both the NBW and low birth weight (LBW) groups, indicating vascular leakage. LBW animals exhibited a lower number of neutrophils, reduced production of interleukin-6 and macrophage-inflammatory protein-2 and decreased upregulation of intercellular adhesion molecule-1 gene expression in lung tissues. Further analysis revealed that the LBW group produced lower levels of prostaglandin-E 2 and failed to secrete leukotriene-B 4 upon LPS stimulation, which correlated with impaired cyclooxygenase-2 and 5-lipoxygenase expression. These results were probably associated with their inability to upregulate the expression of Toll-like receptor-4 and downstream signaling proteins, such as nuclear factor kappa-B, in the lungs. The LBW group also exhibited abnormal airway thickening and high corticosterone levels under basal conditions.
Significance: This study suggests that IUGR-induced foetal programming in LBW offspring threatens HPA axis physiology and corticosterone biodisponibility, and impairs the innate response to bacterial antigens, increasing future susceptibility to pulmonary infection.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
