A Novel Mouse Model of Ureaplasma-Induced Perinatal Inflammation: Effects on Lung and Brain Injury

Normann, Erik; Lacaze‐Masmonteil, Thierry; Eaton, Farah; Schwendimann, Leslie; Gressèns, Pierre; Thébaud, Bernard

doi:10.1203/pdr.0b013e31819984ce

Cited by 86 publications

(91 citation statements)

References 36 publications

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“…In an antenatal mouse model of ureaplasma colonization with signs of perinatal inflammation, there was proinflammatory cytokine activation (MCP-1, IL-1␤, and IL-6) and ureaplasma colonization cleared by postnatal day 3.5 (37). These mice had an increased inflammatory response to hyperoxia relative to uninfected mice (37). In our study, UP exposed lambs and controls had similar PaO 2 and oxygenation, and proinflammatory cytokine mRNA levels were not different.…”

Section: Table 2 Markers Of Lung Inflammation and Injurysupporting

confidence: 48%

Ventilation-Mediated Injury After Preterm Delivery of Ureaplasma parvum Colonized Fetal Lambs

et al. 2010

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Ureaplasma species are the microorganisms most frequently isolated from women with preterm birth and are associated with an increased risk of bronchopulmonary dysplasia. Initiation of ventilation with high tidal volumes (V T ) causes lung injury and inflammation. We investigated whether antenatal colonization with Ureaplasma parvum serovar 3 (UP) would alter the inflammatory response to mechanical ventilation of preterm lambs. Merino ewes were given intraamniotic injections of UP at 55-d gestation, and the lambs were surgically delivered at 128 Ϯ 1 d gestation and assigned to three groups: 1) gentle ventilation (GV), 2) high V T ventilation, or 3) unventilated control. Lambs delivered from noncolonized ewes were assigned to parallel groups. GV lambs received surfactant before ventilation with a V T of 7 mL/kg, positive end expiratory pressure (PEEP) 5 cm H 2 O . High V T lambs received no PEEP and escalating V T to 15 mL/kg by 15 min. At 15 min, surfactant was given, V T was reduced to 7 mL/kg, and PEEP was increased to 5 cm H 2 O. Monocytes in bronchoalveolar lavage were increased by UP, but colonization did not affect lung function. High V T ventilation increased Egr-1 signaling, proinflammatory cytokine expression, and injury scores compared with GV. Antenatal colonization with UP did not change lung function or modulate the lung injury and inflammation caused by high V T ventilation. (Pediatr Res 67: 630-635, 2010)

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Section: Table 2 Markers Of Lung Inflammation and Injurysupporting

confidence: 48%

Ventilation-Mediated Injury After Preterm Delivery of Ureaplasma parvum Colonized Fetal Lambs

et al. 2010

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“…For example, high-dose LPS delivered late in gestation (ED 14-17) induces preterm labor associated with placental and fetal inflammation (38)(39)(40), whereas heat-killed Escherichia coli induces preterm labor and uterine inflammation, without changes in placental or fetal cytokines (41,42). In contrast, infection with Ureaplasma late in gestation induces placental and fetal inflammation without preterm labor (43), whereas viral infection early in gestation (ED 8.5) triggers fetal and maternal splenic inflammation, without inducing placental inflammation or preterm labor (44). In this study, we delivered the Nod1 agonist iE-DAP late in gestation (ED 14.5) and found that, at a high dose of 1000 mg, preterm delivery was induced.…”

Section: Discussionmentioning

confidence: 99%

Nod1 Activation by Bacterial iE-DAP Induces Maternal–Fetal Inflammation and Preterm Labor

Cardenas

Mulla

Myrtolli

et al. 2011

The Journal of Immunology

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There is a strong association between infection and prematurity; however, the underlying mechanisms remain largely unknown. Nod1 and Nod2 are intracellular pattern recognition receptors that are activated by bacterial peptides and mediate innate immunity. We previously demonstrated that human first-trimester trophoblasts express Nod1 and Nod2, which trigger inflammation upon stimulation. This study sought to determine the expression and function of Nod1 and Nod2 in third-trimester trophoblasts, and to characterize the in vivo effects of Nod1 activation on pregnancy outcome. Human term placental tissues and isolated term trophoblast expressed Nod1, but not Nod2. Activation of Nod1 by its agonist, bacterial γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP), in term trophoblast cultures induced a proinflammatory cytokine profile, characterized by elevated levels of secreted IL-6, GRO-α, and MCP-1, when compared with the control. However, these cytokines were not upregulated in response to Nod2 stimulation with bacterial MDP. Administration of high-dose bacterial iE-DAP to pregnant C57BL/6J mice on embryonic day 14.5 triggered preterm delivery within 24 h. iE-DAP at a lower dose that did not induce prematurity, reduced fetal weight, altered the cytokine profile at the maternal–fetal interface, and induced fetal inflammation. Thus, functional Nod1 is expressed by trophoblast cells across gestation and may have a role in mediating infection-associated inflammation and prematurity. This study demonstrates that pattern recognition receptors, other than the TLRs, may be implicated or involved in infection-associated preterm labor.

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“…Hydrogen peroxides are markedly increased in brain tissues of animals exposed to hyperoxia (11). Oxidant stress and systemic inflammation each have independent and synergistic deleterious apoptotic effects on brain microglial cells and immature oligodendrocyte (12)(13)(14). Notably, prolonged supplemental oxygen exposure and systemic inflammation as measured by plasma levels of IL-6 and IL-8 have both been strongly associated with adverse long-term pulmonary and neurodevelopmental outcomes in preterm infants (15)(16)(17)(18)(19).…”

mentioning

confidence: 99%

Inflammatory Response in Preterm Infants Is Induced Early in Life by Oxygen and Modulated by Total Parenteral Nutrition

Lavoie

Watson

et al. 2010

Pediatr Res

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The i.v. lipid emulsion (LIP) is a source of oxidants, which may stimulate inflammation. Coadministration of parenteral multivitamins (MVP) with LIP prevents lipid peroxidation in lightexposed total parenteral nutrition (TPN). We hypothesized that this modality of TPN administration affects systemic inflammation, which may be modulated by exposure to oxygen. Premature infants were allocated to three TPN regimens: control regimen -MVP coadministered with amino acid/dextrose exposed to ambient light, LIP provided separately (n ϭ 9) -LIPϩMVP light exposed (LE): MVP coadministered with light-exposed LIP (n ϭ 9) -LIPϩMVP light protected (LP): MVP coadministered with light-protected LIP (n ϭ 8). In LE and LP, amino acid/dextrose was provided separately. On reaching full TPN, infants were sampled for IL-6 and IL-8 in plasma and the redox potential of glutathione in whole blood (E, mV). Data were compared (ANOVA) in infants exposed to low (Ͻ0. S upplemental oxygen, assisted ventilation, and total parenteral nutrition (TPN) are therapies that expose premature infants to significant oxidant and inflammatory stress (1-4). As these infants are particularly deficient in antioxidant and anti-inflammatory defenses, such therapies may also have potentially harmful long-term effects on their developing lungs and brain (5).Synergistic deleterious effects of inflammation and oxidant stress in preterm infants can occur through a number of potential mechanisms. Exposure to oxygen leads to the accumulation of reactive oxygen species (ROS), which results in the generation of hydrogen and lipid peroxides. When antioxidant defenses are overwhelmed, this reaction self-propagates, and the peroxides generated can damage cells and tissues (6). In preterm infants, even brief periods of supplemental oxygen at birth may produce sufficient oxidant stress to cause sustained lung disease (7). Also, oxidized lipids and hydrogen peroxides have a direct modulatory effect on inflammatory pathways, including Toll-like receptors (8), and the transcriptional activator nuclear factor (NF)-kB (9). Such a direct activation of inflammatory pathways by oxygen byproducts can potentiate inflammatory responses and promote further endothelial injury and pulmonary capillary leakage, resulting in systemic generalization of the inflammation with potentially harmful consequences on the developing preterm brain (10). Hydrogen peroxides are markedly increased in brain tissues of animals exposed to hyperoxia (11). Oxidant stress and systemic inflammation each have independent and synergistic deleterious apoptotic effects on brain microglial cells and immature oligodendrocyte (12)(13)(14). Notably, prolonged supplemental oxygen exposure and systemic inflammation as measured by plasma levels of IL-6 and IL-8 have both been strongly associated with adverse long-term pulmonary and neurodevelopmental outcomes in preterm infants (15)(16)(17)(18)(19).Quality of nutrition early in life has documented beneficial effects on health outcomes later in life (20). Premature...

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A Novel Mouse Model of Ureaplasma-Induced Perinatal Inflammation: Effects on Lung and Brain Injury

Cited by 86 publications

References 36 publications

Ventilation-Mediated Injury After Preterm Delivery of Ureaplasma parvum Colonized Fetal Lambs

Ventilation-Mediated Injury After Preterm Delivery of Ureaplasma parvum Colonized Fetal Lambs

Nod1 Activation by Bacterial iE-DAP Induces Maternal–Fetal Inflammation and Preterm Labor

Inflammatory Response in Preterm Infants Is Induced Early in Life by Oxygen and Modulated by Total Parenteral Nutrition

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