Activation of toll-like receptors 2 or 3 and preterm delivery in the mouse.
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 beta and chemokine (C-C motif) ligand 5 (CCL5, also known as RANTES) but not interleukin 1beta, 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 beta and the chemokine CCL5 in uterine tissues but not in fetal membranes.
Ilievski
Vladimir
V
Department of Obstetrics and Gynecology, Evanston Northwestern Healthcare, Evanston, Illinois 60201, USA.
Lu
Shi-Jiang
SJ
Hirsch
Emmet
E
D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D010457:Peptidoglycan / Q000494:pharmacology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D013682:Teichoic Acids / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051196:Toll-Like Receptor 3 / Q000235:genetics*
D008070:Lipopolysaccharides; D010457:Peptidoglycan; C519703:TLR3 protein, mouse; D013682:Teichoic Acids; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; C009900:lipoteichoic acid