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Citations to this article

Maternal regulation of inflammatory cues is required for induction of preterm birth
Monica Cappelletti, … , Tamara Tilburgs, Senad Divanovic
Monica Cappelletti, … , Tamara Tilburgs, Senad Divanovic
Published November 19, 2020
Citation Information: JCI Insight. 2020;5(22):e138812. https://doi.org/10.1172/jci.insight.138812.
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Research Article Inflammation Article has an altmetric score of 2

Maternal regulation of inflammatory cues is required for induction of preterm birth

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Abstract

Infection-driven inflammation in pregnancy is a major cause of spontaneous preterm birth (PTB). Both systemic infection and bacterial ascension through the vagina/cervix to the amniotic cavity are strongly associated with PTB. However, the contribution of maternal or fetal inflammatory responses in the context of systemic or localized models of infection-driven PTB is not well defined. Here, using intraperitoneal or intraamniotic LPS challenge, we examined the necessity and sufficiency of maternal and fetal Toll-like receptor (TLR) 4 signaling in induction of inflammatory vigor and PTB. Both systemic and local LPS challenge promoted induction of inflammatory pathways in uteroplacental tissues and induced PTB. Restriction of TLR4 expression to the maternal compartment was sufficient for induction of LPS-driven PTB in either systemic or intraamniotic challenge models. In contrast, restriction of TLR4 expression to the fetal compartment failed to induce LPS-driven PTB. Vav1-Cre–mediated genetic deletion of TLR4 suggested a critical role for maternal immune cells in inflammation-driven PTB. Further, passive transfer of WT in vitro–derived macrophages and dendritic cells to TLR4-null gravid females was sufficient to induce an inflammatory response and drive PTB. Cumulatively, these findings highlight the critical role for maternal regulation of inflammatory cues in induction of inflammation-driven parturition.

Authors

Monica Cappelletti, Jessica R. Doll, Traci E. Stankiewicz, Matthew J. Lawson, Vivien Sauer, Bingqiang Wen, Vladimir V. Kalinichenko, Xiaofei Sun, Tamara Tilburgs, Senad Divanovic

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Total citations by year

Year: 2025 2024 2023 2022 2021 Total
Citations: 3 3 7 7 4 24
Citation information
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Citations to this article (24)

Title and authors Publication Year
N,N-dimethylacetamide blocks inflammation-induced preterm birth and remediates maternal systemic immune responses
Reznik SE, Kashou A, Ward D, Yellon SM
bioRxiv 2025
N,N-dimethylacetamide blocks inflammation-induced preterm birth and remediates maternal systemic immune responses
Reznik SE, Kashou A, Ward D, Yellon SM
Scientific Reports 2025
A Broad-Spectrum Chemokine Inhibitor Drives M2 Macrophage Polarization Through Modulation of the Myometrial Secretome
Boros-Rausch A, Dorogin A, Nadeem L, Shynlova O, Lye SJ
Cells 2025
Deciphering maternal-fetal crosstalk in the human placenta during parturition using single-cell RNA sequencing
Garcia-Flores V, Romero R, Tarca AL, Peyvandipour A, Xu Y, Galaz J, Miller D, Chaiworapongsa T, Chaemsaithong P, Berry SM, Awonuga AO, Bryant DR, Pique-Regi R, Gomez-Lopez N
Science Translational Medicine 2024
Biological and behavioral pathways from prenatal depression to offspring cardiometabolic risk: Testing the developmental origins of health and disease hypothesis.
Doom JR, Deer LK, Dabelea D, LeBourgeois MK, Lumeng JC, Martin CK, Hankin BL, Davis EP
Developmental Psychology 2024
Predictors of Inflammation-Mediated Preterm Birth
Georges HM, Norwitz ER, Abrahams VM
Physiology (Bethesda, Md.) 2024
BAFF and APRIL counterregulate susceptibility to inflammation-induced preterm birth
Jessica R. Doll, Maria Moreno-Fernandez, Traci Stankiewicz, Jennifer Wayland, Adrienne Wilburn, Claire Chougnet, Daniela Giordano, Monica Cappelletti, Pietro Presicce, Suhas Kallapur, Nathan Salomonis, Tamara Tilburgs, Senad Divanovic
Cell Reports 2023
Stromal cells-specific retinoic acid determines parturition timing at single-cell and spatial-temporal resolution
Zhao H, Wang Y, Xu H, Liu M, Xu X, Zhu S, Liu Z, Cai H, Wang Y, Lu J, Yang X, Kong S, Bao H, Wang H, Deng W
iScience 2023
A key role for NLRP3 signaling in preterm labor and birth driven by the alarmin S100B
Galaz J, Motomura K, Romero R, Liu Z, Garcia-Flores V, Tao L, Xu Y, Done B, Arenas-Hernandez M, Kanninen T, Farias-Jofre M, Miller D, Tarca AL, Gomez-Lopez N
Translational research : the journal of laboratory and clinical medicine 2023
Protocol for cytokine and uterine immune cell characterization in a mouse model of LPS-induced preterm birth
Wayland JL, Stemen EL, Doll JR, Divanovic S
2023
Elevated expression of Toll-like receptor 4 and cytokines in both serum and myometrium at term may serve as promising biomarkers for uterine activation preceding labor
Chen Z, Li J, Xu W, Wu X, Xiang F, Li X, Zhang M, Zheng J, Kang X, Wu R
Frontiers in Endocrinology 2023
Deciphering a critical role of uterine epithelial SHP2 in parturition initiation at single cell resolution
Liu M, Ji M, Cheng J, Li Y, Tian Y, Zhao H, Wang Y, Zhu S, Zhang L, Xu X, Feng GS, Liang X, Bao H, Tang Y, Kong S, Lu J, Wang H, Lu Z, Deng W
Nature Communications 2023
Maternal Vaccination to Prevent Adverse Pregnancy Outcomes: An Underutilized Molecular Immunological Intervention?
Giles ML, Way SS, Marchant A, Aghaepour N, James T, Schaltz-Buchholzer F, Zazara D, Arck P, Kollmann TR
Journal of molecular biology 2023
Placental dysfunction influences fetal monocyte subpopulation gene expression in preterm birth
Abhineet M Sharma, Robert Birkett, Erika T. Lin, Linda M. Ernst, William A Grobman, Suchitra Swaminathan, Hiam Abdala-Valencia, Alexander V. Misharin, Elizabeth T Bartom, Karen Mestan
JCI Insight 2022
Fetal and maternal NLRP3 signaling is required for preterm labor and birth
Kenichiro Motomura, Roberto Romero, Jose Galaz, Li Tao, Valeria Garcia-Flores, Yi Xu, Bogdan Done, Marcia Arenas-Hernandez, Derek Miller, Pedro Gutierrez-Contreras, Marcelo Farias-Jofre, Siddhesh Aras, Lawrence I. Grossman, Adi L Tarca, Nardhy Gomez-Lopez
JCI Insight 2022
Prenatal inflammation causes obesity and abnormal lipid metabolism via impaired energy expenditure in male offspring
M Ni, Q Zhang, J Zhao, D Yao, T Wang, Q Shen, W Li, B Li, X Ding, Z Liu
Nutrition & Metabolism 2022
The Lung Microenvironment Instructs Gene Transcription in Neonatal and Adult Alveolar Macrophages
A Honda, M Hoeksema, M Sakai, S Lund, O Lakhdari, L Butcher, T Rambaldo, N Sekiya, C Nasamran, K Fisch, E Sajti, C Glass, L Prince
Journal of immunology (Baltimore, Md. : 1950) 2022
Emerging role of toll-like receptors signaling and its regulators in preterm birth: a narrative review.
Huang G, Yao D, Yan X, Zheng M, Yan P, Chen X, Wang D
Archives of Gynecology and Obstetrics 2022
RAC1 is involved in uterine myometrium contraction in the inflammation-associated preterm birth
Diao M, Zhou J, Tao Y, Hu Z, Lin X
Reproduction (Cambridge, England) 2022
Term and Preterm Birth Initiation Is Associated with the Macrophages Shifting to M1 Polarization in Gestational Tissues in Mice.
Shan Y, Shen S, Long J, Tang Z, Wu C, Ni X
Biology 2022
Macrophages exert homeostatic actions in pregnancy to protect against preterm birth and fetal inflammatory injury
Nardhy Gomez-Lopez, Valeria Garcia-Flores, Peck Y Chin, Holly M Groome, Melanie T. Bijland, Kerrilyn R. Diener, Roberto Romero, Sarah A Robertson
JCI Insight 2021
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EJ Gregory, J Liu, H Miller-Handley, JM Kinder, SS Way
Frontiers in immunology 2021
The induction of preterm labor in rhesus macaques is determined by the strength of immune response to intrauterine infection
M Cappelletti, P Presicce, M Feiyang, P Senthamaraikannan, LA Miller, M Pellegrini, MS Sim, AH Jobe, S Divanovic, SS Way, CA Chougnet, SG Kallapur, GC Smith
PLoS Biology 2021
Composition of Vaginal Microbiota in Pregnant Women With Aerobic Vaginitis
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Frontiers in Cellular and Infection Microbiology 2021

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