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Omega-3 fatty acids suppress Fusobacterium nucleatum–induced placental inflammation originating from maternal endothelial cells
Jeewon Garcia-So, … , Kang Liu, Yiping W. Han
Jeewon Garcia-So, … , Kang Liu, Yiping W. Han
Published February 7, 2019
Citation Information: JCI Insight. 2019;4(3):e125436. https://doi.org/10.1172/jci.insight.125436.
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Research Article Microbiology

Omega-3 fatty acids suppress Fusobacterium nucleatum–induced placental inflammation originating from maternal endothelial cells

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Abstract

Fusobacterium nucleatum is an oral anaerobe prevalent in intrauterine infection associated with a wide spectrum of adverse pregnancy outcomes. We demonstrate here that F. nucleatum triggers placental inflammation through maternal, rather than paternal, TLR4-mediated signaling. Elimination of TLR4 from maternal endothelial cells alleviated placental inflammation and reduced fetal and neonatal death, while elimination of TLR4 in the hematopoietic cells had no effect. The placental inflammatory response followed a spatiotemporal pattern, with NF-κB activation observed first in the maternal endothelial cells and then in the decidual cells surrounding the endothelium, followed by induction of inflammatory cytokines and chemokines. Supplementation of pregnant mice with fish oil as a source of omega-3 fatty acids suppressed placental inflammation, reduced F. nucleatum proliferation in the placenta, and increased fetal and neonatal survival. In vitro analysis illustrates that omega-3 fatty acids inhibit bacterial-induced inflammatory responses from human umbilical cord endothelial cells. Our study therefore reveals a mechanism by which microbial infections affect pregnancy and identifies a prophylactic therapy to protect against intrauterine infections.

Authors

Jeewon Garcia-So, Xinwen Zhang, Xiaohua Yang, Mara Roxana Rubinstein, De Yu Mao, Jan Kitajewski, Kang Liu, Yiping W. Han

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Figure 4

Purified omega-3 fatty acids suppress endothelial inflammation induced by F. nucleatum.

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Purified omega-3 fatty acids suppress endothelial inflammation induced b...
Purified omega-3 (300 μM or 600 μM) or omega-6 fatty acids (600 μM) were complexed with fatty acid–free BSA at a molar ratio of 4:1 and preincubated with HUVECs for 3 hours prior to bacterial infection. Log-phase F. nucleatum was incubated with primary HUVECs at an MOI of 50:1 for 24 hours. Levels of mRNA were measured by real-time quantitative PCR and are expressed as fold change compared to the uninfected control group. Each experiment was performed in triplicates and repeated at least 3 times. The results are presented as dot plots with average and SEM. One-way ANOVA was performed with Bonferroni post-test. **P < 0.01, ***P < 0.001, ****P < 0.0001.

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