The role of toll-like receptors (TLR-2 and -4) and triggering receptor expressed on myeloid cells 1 (TREM-1) in human term and preterm labor.
OBJECTIVE
To define the role of Toll-like receptors (TLR-2, TLR-4) and triggering receptor expressed on myeloid cells-1 (TREM-1) in pregnant human myometrium.


METHODS
Expression of TLR-2 and -4 mRNA and protein and TREM-1 mRNA was quantified in human myometrial samples. Subsequently, we investigated the effect of medroxyprogesterone acetate (MPA) as a functional inhibitor of the TLR agonist lipopolysaccharide (LPS).


RESULTS
Messenger RNA expression of TLR-2 and -4 was significantly higher in myometrium at term compared with preterm (P = .009 and .016, respectively). Toll-like receptor-2 protein expression was significantly higher during labor (P = .002) compared with nonlaboring samples. Triggering receptor expressed on myeloid cells-1 mRNA expression was increased in both myometrium and cervix after labor at term (P < .05). Medroxyprogesterone acetate significantly suppressed LPS-induced production of interleukin 1b (IL-1b), IL-6, and IL-8 in vitro (P < .05).


CONCLUSIONS
Toll-like receptors 2and 4 and TREM-1 are expressed in human myometrium and may play a role in the mechanism of labor at term, and their functional effects are inhibited by MPA.
Youssef
Refaat E
RE
Ninewells Hospital and School of Medicine, Dundee, United Kingdom. ryoussef@nhs.net
Ledingham
Marie Anne
MA
Bollapragada
Shrikant S
SS
O'Gorman
Neil
N
Jordan
Fiona
F
Young
Anne
A
Norman
Jane E
JE
D000328:Adult; D001706:Biopsy; D003271:Contraceptive Agents, Female / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D022423:Myeloid Cells / Q000187:drug effects / Q000502:physiology; D009215:Myometrium / Q000166:cytology / Q000502:physiology*; D007752:Obstetric Labor, Premature / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D011247:Pregnancy; D046509:Tissue Culture Techniques; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
D003271:Contraceptive Agents, Female; D008070:Lipopolysaccharides; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D017258:Medroxyprogesterone Acetate