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. CONCLUSION: NAC may be beneficial in prevention of MIA-related preterm birth through attenuation of NF-κB activation and COX-2 upregulation.
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. CONCLUSION:NAC may be beneficial in prevention of MIA-related preterm birth through attenuation of NF-κB activation and COX-2 upregulation.
Authors: Monica Cappelletti; Pietro Presicce; Matthew J Lawson; Vandana Chaturvedi; Traci E Stankiewicz; Simone Vanoni; Isaac Tw Harley; Jaclyn W McAlees; Daniel A Giles; Maria E Moreno-Fernandez; Cesar M Rueda; Paranth Senthamaraikannan; Xiaofei Sun; Rebekah Karns; Kasper Hoebe; Edith M Janssen; Christopher L Karp; David A Hildeman; Simon P Hogan; Suhas G Kallapur; Claire A Chougnet; Sing Sing Way; Senad Divanovic Journal: JCI Insight Date: 2017-03-09
Authors: Lauren Anton; Luz-Jeannette Sierra; Ann DeVine; Guillermo Barila; Laura Heiser; Amy G Brown; Michal A Elovitz Journal: Front Microbiol Date: 2018-10-08 Impact factor: 5.640