N-acetylcysteine prevents preterm birth by attenuating the LPS-induced expression of contractile associated proteins in an animal model.
OBJECTIVE
Intrauterine infection is associated with maternal immune activation (MIA) leading to preterm birth through upregulation of contractile associated proteins (CAPs). We hypothesized that N-acetylcysteine would decrease NF-κB activation and CAP expression in a MIA model for preterm birth.


METHODS
Pregnant CD-1 mice were given intrauterine LPS or saline on day 15/20. They received NAC or saline prior to injection and were monitored until delivery. The rate of preterm birth in the control, LPS, and LPS + NAC animals was determined. In another group, animals were sacrificed 6 h after treatment and myometrium was collected. COX-2, connexin 43, and oxytocin receptor expression was determined.


RESULTS
LPS administration resulted in preterm birth and this effect was attenuated by NAC. LPS increased COX-2, connexin 43, and oxytocin receptor expression. NAC significantly decreased COX-2 expression. LPS increased NF-κB activation; this was attenuated by NAC.


CONCLUSIONS
NAC may be beneficial in prevention of MIA-related preterm birth through attenuation of NF-κB activation and COX-2 upregulation.
Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Medical University of South Carolina, Charleston, SC 29492, USA. changey@musc.edu
Eugene Y
EY
Chang
Jingmei
J
Zhang
Scott
S
Sullivan
Roger
R
Newman
Inderjit
I
Singh
D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D003285:Contractile Proteins / Q000235:genetics* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D023421:Models, Animal; D008954:Models, Biological; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism; D014590:Uterine Contraction / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014599:Uterus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D018031:Connexin 43; D003285:Contractile Proteins; C543076:GJA1 protein, mouse; D008070:Lipopolysaccharides; D016328:NF-kappa B; C576074:OXTR protein, mouse; D018045:Receptors, Oxytocin; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D000111:Acetylcysteine