Disruption of Interleukin-18, but Not Interleukin-1, Increases Vulnerability to Preterm Delivery and Fetal Mortality after Intrauterine Inflammation

191

177

Section: Discussionmentioning

confidence: 91%

IL-1 Receptor Antagonist Protects against Placental and Neurodevelopmental Defects Induced by Maternal Inflammation

Girard

Tremblay

Lepage

et al. 2010

191

177

“…The genotype of mice was determined by PCR of genomic DNA obtained from mouse tails, as previously described (12,13). The WT allele was detected using the forward primer (5Ј-TGGCATGCCTCCATCATAGT TAACC-3Ј) and the reverse primer (5Ј-GTCAGAAACAACCACCAC CATGC-3Ј), and the mutant allele detected using the forward primer (5Ј-TGGCATGCCTCCATCATAGTTAACC-3Ј) and the reverse primer (5Ј-ATCGCCTTCTATCGCCTTCTTGACG-3Ј).…”

Section: Genotypingmentioning

confidence: 99%

Lipopolysaccharide Sensitizes Neonatal Hypoxic-Ischemic Brain Injury in a MyD88-Dependent Manner

Wang

Stridh

et al. 2009

Self Cite

153

143

Neurological deficits in children, including cerebral palsy, are associated with prior infection during the perinatal period. Experimentally, we have shown that pre-exposure to the Gram-negative component LPS potentiates hypoxic-ischemic (HI) brain injury in newborn animals. LPS effects are mediated by binding to TLR4, which requires recruitment of the MyD88 adaptor protein or Toll/IL-1R domain-containing adapter inducing IFN-β for signal transduction. In this study, we investigated the role of MyD88 in neonatal brain injury. MyD88 knockout (MyD88 KO) and wild-type mice were subjected to left carotid artery ligation and 10% O2 for 50 min on postnatal day 9. LPS or saline were administered i.p. at 14 h before HI. At 5 days after HI in wild-type mice, LPS in combination with HI caused a significant increase in gray and white matter tissue loss compared with the saline-HI group. By contrast, in the MyD88 KO mice there was no potentiation of brain injury with LPS-HI. MyD88 KO mice exhibited reduced NFκB activation and proinflammatory cytokine-chemokine expression in response to LPS. The number of microglia and caspase-3 activation was increased in the brain of MyD88 KO mice after LPS exposure. Collectively, these findings indicate that MyD88 plays an essential role in LPS-sensitized HI neonatal brain injury, which involves both inflammatory and caspase-dependent pathways.

“…Up to 30% of cases of spontaneous preterm birth are associated with intrauterine microbial colonization or histological evidence of chorioamnionitis. Intraamniotic inflammation is found in approximately half of the cases of preterm labor and premature preterm rupture of membranes (7). The presence of intrauterine inflammation is not only a cause of preterm birth but is also associated with an increase in neonatal morbidity and mortality.…”

mentioning

confidence: 99%

Depletion of Invariant NKT Cells Reduces Inflammation-Induced Preterm Delivery in Mice

Fang

Dong

et al. 2012

This study sought to determine whether invariant NKT (iNKT) cells play an essential role in inflammation-induced preterm delivery. Preterm delivery and fetal death rates were determined in wild-type (WT) C57BL/6 mice and iNKT cell-deficient Jα18−/− mice injected i.p. with LPS. The percentages of decidual immune cells, including activated subsets, and costimulatory molecule expression were analyzed by flow cytometry. Th1 and Th2 cytokine production in the culture supernatants of decidual mononuclear cells was measured by ELISA. To some extent, Jα18−/− mice were resistant to LPS-induced preterm delivery. The proportions of decidual CD3+ and CD49b+ cells were slightly lower in Jα18−/− mice than in WT Jα18+/+ mice, whereas almost no CD3+CD49b+ cells could be found in Jα18-null mice. The percentages of activated decidual DCs, T cells, and NK cells were significantly lower in LPS-treated Jα18−/− mice than in WT mice. The CD40, CD80, and CD86 expression levels on decidual CD11c+ cells from Jα18−/− mice were also significantly lower than in WT mice. Mean concentrations of Th1 cytokines IFN-γ and IL-12p70 in the culture supernatants of decidual mononuclear cells from LPS-treated Jα18−/− mice were apparently lower than those of LPS-induced WT mice. Additionally, the proportions of activated CD11c+ cells, CD3+ cells, and CD49b+ cells in LPS-induced preterm delivery mice were strikingly higher in both WT and null mice when compared with the control PBS group and LPS-injected but normally delivered mice. Our results suggest that iNKT cells may play an essential role in inflammation-induced preterm birth.