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Activation of Toll-like Receptors 2 or 3 and Preterm Delivery in the Mouse

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Abstract

The objective of this study is to test whether the activation of toll-like receptors (TLRs) 2 and 3 (innate immune receptors for gram-positive and viral pathogens, respectively) can induce preterm delivery. One uterine horn of preterm pregnant CD-1 mice at approximately 75% of gestation was injected with TLR-2 ligands (lipoteichoic acid [LTA] or peptidoglycan [PGN]) or the TLR-3 ligand polyinosinic:cytidylic acid (poly[I:C]). Preterm delivery was recorded. In a separate group of mice, tissue mRNAs were quantified by reverse transcriptase polymerase chain reaction 5 hours after treatment with PGN or poly(I:C). Intrauterine PGN and LTA induced preterm delivery, reaching 100% at maximal doses. Intraperitoneal PGN also induced preterm delivery but at lower rates (maximum = 55%). Intrauterine poly(I:C) induced preterm birth in up to 31% of mice. Poly(I:C) induced uterine interferon β and chemokine (C-C motif) ligand 5 (CCL5, also known as RANTES) but not interleukin 1 β, tumor necrosis factor, or lipopolysaccharide-induced CXC chemokine. PGN did not alter these mRNAs when compared with saline. Neither treatment induced gene expression in fetal membranes. Activation of either TLR-2 or -3 can induce preterm delivery in the mouse. Activation of TLR-3 with poly(I:C) induces interferon β and the chemokine CCL5 in uterine tissues but not in fetal membranes.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Evanston Northwestern Healthcare, 2650 Ridge Avenue, Evanston, Illinois, 60201, USA

    Vladimir Ilievski MD & Emmet Hirsch MD

  2. Advanced Cell Technology, Worchester, Massachusetts, USA

    Shi-Jiang Lu PhD

  3. Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

    Emmet Hirsch MD

Authors
  1. Vladimir Ilievski MD
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  2. Shi-Jiang Lu PhD
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  3. Emmet Hirsch MD
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Corresponding author

Correspondence to Emmet Hirsch MD.

Additional information

This work was funded in part by 1RO1HD41689. We thank Lennard Wahlberg for technical assistance.

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Ilievski, V., Lu, SJ. & Hirsch, E. Activation of Toll-like Receptors 2 or 3 and Preterm Delivery in the Mouse. Reprod. Sci. 14, 315–320 (2007). https://doi.org/10.1177/1933719107302959

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  • DOI: https://doi.org/10.1177/1933719107302959

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