Regulation of apoptosis and innate immune stimuli in inflammation-induced preterm labor.
J Immunol
; 191(11): 5702-13, 2013 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-24163412
ABSTRACT
An innate immune response is required for successful implantation and placentation. This is regulated, in part, by the a2 isoform of V-ATPase (a2V) and the concurrent infiltration of M1 (inflammatory) and M2 (anti-inflammatory) macrophages to the uterus and placenta. The objective of the present study was to identify the role of a2V during inflammation-induced preterm labor in mice and its relationship to the regulation of apoptosis and innate immune responses. Using a mouse model of infection-induced preterm delivery, gestational tissues were collected 8 h after intrauterine inoculation on day 14.5 of pregnancy with either saline or peptidoglycan (PGN; a TLR 2 agonist) and polyinosinic-polycytidylic acid [poly(IC); a TLR3 agonist], modeling Gram-positive bacterial and viral infections, respectively. Expression of a2V decreased significantly in the placenta, uterus, and fetal membranes during PGN+poly(IC)-induced preterm labor. Expression of inducible NO synthase was significantly upregulated in PGN+poly(IC)-treated placenta and uterus. PGN+poly(IC) treatment disturbed adherens junction proteins and increased apoptotic cell death via an extrinsic pathway of apoptosis among uterine decidual cells and spongiotrophoblasts. F4/80(+) macrophages were increased and polarization was skewed in PGN+poly(IC)-treated uterus toward double-positive CD11c(+) (M1) and CD206(+) (M2) cells, which are critical for the clearance of dying cells and rapid resolution of inflammation. Expression of Nlrp3 and activation of caspase-1 were increased in PGN+poly(IC)-treated uterus, which could induce pyroptosis. These results suggest that the double hit of PGN+poly(IC) induces preterm labor via reduction of a2V expression and simultaneous activation of apoptosis and inflammatory processes.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Placenta
/
Útero
/
ATPasas de Translocación de Protón
/
Trabajo de Parto Prematuro
/
Macrófagos
Tipo de estudio:
Etiology_studies
Límite:
Animals
/
Female
/
Humans
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Pregnancy
Idioma:
En
Revista:
J Immunol
Año:
2013
Tipo del documento:
Article