Expression and activity of Toll-like receptors 1-9 in the human term placenta and changes associated with labor at term.
Inflammatory processes are involved in the initiation and maintenance of labor, suggesting that Toll-like receptor (TLR) activity within gestation-associated tissues, such as the placenta, might contribute to the process of parturition. Expression of transcripts for TLR1-TLR10 was examined in term (>37 wk of gestation) human placentas collected in the absence of labor (elective caesarean sections; ECS; n = 11) and after the completion of labor (normal vaginal delivery; NVD; n = 12). Placental explants were cultured in the presence of agonists for TLR2, TLR3, TLR4, TLR5, TLR7, TLR8, and TLR9, and cytokine production after 24 h was examined. All placentas expressed transcripts for TLR1-TLR10. Reactivity to all agonists except CpG oligonucleotides was observed, indicating that, other than TLR9, all of the receptors studied yielded functional responses. Placental explants prepared from NVD placentas (n = 17) produced significantly more TNFA in response to lipopolysaccharide (TLR4 agonist) and resiquimod (TLR7/8 agonist) than explants from ECS placentas (n = 17). In contrast, gene expression analysis revealed that only transcripts for TLR2 and TLR5 were significantly elevated in association with labor. The human term placenta expresses a variety of functional TLRs, indicating that this family of receptors has an important role in parturition via as yet undetermined cell types and signaling pathways.
Patni
Shalini
S
Princess of Wales Maternity Unit, Birmingham Heartlands Hospital, Birmingham B9 5SS, United Kingdom.
Wynen
Louise P
LP
Seager
Anna L
AL
Morgan
Gareth
G
White
John O
JO
Thornton
Catherine A
CA
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007743:Labor, Obstetric / Q000235:genetics* / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D047929:Term Birth / Q000235:genetics* / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D055815:Young Adult
D016207:Cytokines; D007093:Imidazoles; D008024:Ligands; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; C402365:resiquimod