Differential fetal and maternal contributions to the cytokine milieu in a murine model of infection-induced preterm birth

1998 ◽  
Vol 5 (1) ◽  
pp. 62A-62A
Author(s):  
E HIRSCH ◽  
S MEHTA ◽  
R BLANCHARD
2022 ◽  
Vol 226 (1) ◽  
pp. S9
Author(s):  
Katherine M. Leonard ◽  
Elisabeth Dornisch ◽  
Jennifer Damicis ◽  
Irina Burd ◽  
Jason Pates ◽  
...  

2012 ◽  
Vol 119 ◽  
pp. S263-S263
Author(s):  
K. Abhichandani ◽  
N. Shah ◽  
S. Sundaram ◽  
C.-H. Chen ◽  
H. Yen ◽  
...  
Keyword(s):  

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Sarah M. Estrada ◽  
Andrew S. Thagard ◽  
Mary J. Dehart ◽  
Jennifer R. Damicis ◽  
Elisabeth M. Dornisch ◽  
...  

AbstractPrematurity is associated with perinatal neuroinflammation and injury. Screening for genetic modulators in an LPS murine model of preterm birth revealed the upregulation of Nr4a1, an orphan nuclear transcription factor that is normally absent or limited in embryonic brains. Concurrently, Nr4a1 was downregulated with magnesium sulfate (MgSO4) and betamethasone (BMTZ) treatments administered to LPS exposed dams. To understand the role of Nr4a1 in perinatal brain injury, we compared the preterm neuroinflammatory response in Nr4a1 knockout (KO) versus wild type (wt) mice. Key inflammatory factors Il1b, Il6 and Tnf, and Iba1+ microglia were significantly lower in Nr4a1 KO versus wt brains exposed to LPS in utero. Treatment with MgSO4/BMTZ mitigated the neuroinflammatory process in wt but not Nr4a1 KO brains. These results correspond with a reduction in cerebral hemorrhage in wt but not mutant embryos from dams given MgSO4/BMTZ. Further analysis with Nr4a1-GFP-Cre × tdTomato loxP reporter mice revealed that the upregulation of Nr4a1 with perinatal neuroinflammation occurs in the cerebral vasculature. Altogether, this study implicates Nr4a1 in the developing vasculature as a potent mediator of neuroinflammatory brain injury that occurs with preterm birth. It is also possible that MgSO4/BMTZ mitigates this process by direct or indirect inhibition of Nr4a1.


2021 ◽  
Author(s):  
Zeng-Hui Wei ◽  
Oluwabukola Salami ◽  
Jagadish Koya ◽  
Swapna Munnangi ◽  
Ryan Pekson ◽  
...  

Abstract Preterm birth accounts for the majority of perinatal mortality worldwide and there remains no FDA-approved drug to prevent it. Recently, we discovered that the common drug excipient, N,N-dimethylacetamide (DMA), prevents inflammation–induced preterm birth in mice by inhibiting NF-κB. Since we reported this finding it has come to light that a group of widely used, structurally related aprotic solvents, including DMA, N-methyl-2-pyrrolidone (NMP) and dimethylformamide (DMF), have anti-inflammatory efficacy. We show here that DMF suppresses LPS-induced TNFα secretion from RAW 264.7 cells and IL-6 and IL-8 secretion from HTR-8 cells at concentrations that do not significantly affect cell viability. In vivo, DMF decreases LPS-induced inflammatory cell infiltration and expression of TNFα and IL-6 in the placental labyrinth, all to near baseline levels. Finally, DMF decreases the rate of preterm birth in LPS-induced pregnant mice (P<.0001) and the rate at which pups are spontaneously aborted (P<.0001). In summary, DMF, a widely used solvent structurally related to DMA and NMP, prevents LPS-induced preterm birth in a murine model without overt toxic or teratogenic effects. Re-purposing the DMA/DMF/NMP family of small molecules as anti-inflammatory drugs is a promising new approach to preventing inflammation–induced preterm birth and potentially other inflammatory disorders as well.


2010 ◽  
Vol 13 (4) ◽  
pp. 273-281 ◽  
Author(s):  
Linda M. Ernst ◽  
Juan Gonzalez ◽  
Ella Ofori ◽  
Michal Elovitz

2020 ◽  
Vol 190 (2) ◽  
pp. 295-305 ◽  
Author(s):  
Hannah C. Zierden ◽  
Jairo I. Ortiz Ortiz ◽  
Peter Dimitrion ◽  
Victoria Laney ◽  
Sabrine Bensouda ◽  
...  
Keyword(s):  

2015 ◽  
Vol 185 (3) ◽  
pp. 862-869 ◽  
Author(s):  
Vibhuti Vyas ◽  
Charles R. Ashby ◽  
Nicole S. Olgun ◽  
Sruthi Sundaram ◽  
Oluwabukola Salami ◽  
...  

2012 ◽  
Vol 206 (1) ◽  
pp. S219
Author(s):  
James Kurtzman ◽  
Jeeyoon Park ◽  
Joseph Elsissy ◽  
Ryan Strilaeff ◽  
Robert Garfield ◽  
...  

2017 ◽  
Vol 25 (5) ◽  
pp. 662-673 ◽  
Author(s):  
Tianbing Ding ◽  
Lauren A. Lambert ◽  
David M. Aronoff ◽  
Kevin G. Osteen ◽  
Kaylon L. Bruner-Tran

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