title: Carbon monoxide attenuates bacteria-induced Endothelin-1 expression in second trimester placental explants.
abstract: BACKGROUND
  The pro-inflammatory mediator and potent vasoconstrictor Endothelin-1 (ET-1) is known to be expressed in the placenta. We have recently demonstrated that very low, non-toxic doses of carbon monoxide (CO), prevented infection-induced preterm birth in mice. However the effect(s) of CO on human gestational tissues is yet to be fully explored. We hypothesize that CO will have a protective role against inflammation-induced E. coli by down-regulating the ET axis in placental explants.
  
  
  METHODS
  Twenty placentas from elective termination of pregnancy in the second trimester were analyzed with or without exposure to heat killed E. coli over the course of 30 h. Placental ET-1, along with its biologically inactive precursor Big ET-1, and Endothelin Converting Enzyme-1 (ECE-1, responsible for the cleavage of Big ET-1 to ET-1), were analyzed by ELISA. Gene expression for ET-1 (EDN1), ECE-1 and the ETA receptor (EDNRA) were analyzed using qPCR. Localization of ET-1 expression was also demonstrated using immunohistochemistry.
  
  
  RESULTS
  E. coli significantly increased ET-1 transcription and secretion of BIG ET-1 and ET-1 in a time dependant manner which was ameliorated when exposed to CO at later time points. In the presence of CO, mRNA levels of ECE-1 were significantly reduced at 3 and 24 h, while EDNRA was significantly reduced at 6 and 18 h.
  
  
  CONCLUSIONS
  Up-regulation of ET-1 production in human placenta in the setting of infection can be attenuated by low doses of CO. Our results further explore the anti-inflammatory and regulatory mechanism(s) of CO on the ET axis components at the maternal fetal interface.
authors.affiliation: Women and Children's Research Laboratory, Winthrop University Hospital, Mineola, NY 11501, USA. Electronic address: nolgun@winthrop.org.
authors.forename: N S
authors.initials: NS
authors.lastname: Olgun
authors.affiliation: Women and Children's Research Laboratory, Winthrop University Hospital, Mineola, NY 11501, USA. Electronic address: yarita22@hotmail.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Arita
authors.affiliation: Women and Children's Research Laboratory, Winthrop University Hospital, Mineola, NY 11501, USA. Electronic address: monicahanna96@yahoo.com.
authors.forename: M
authors.initials: M
authors.lastname: Hanna
authors.affiliation: Department of Obstetrics & Gynecology, NYU School of Medicine, New York, NY, USA. Electronic address: amitasrigowri.murthy@nyumc.org.
authors.forename: A
authors.initials: A
authors.lastname: Murthy
authors.affiliation: Department of Obstetrics & Gynecology, NYU School of Medicine, New York, NY, USA. Electronic address: sigrid.tristan@nyumc.org.
authors.forename: S
authors.initials: S
authors.lastname: Tristan
authors.affiliation: Women and Children's Research Laboratory, Winthrop University Hospital, Mineola, NY 11501, USA; Department of Obstetrics and Gynecology, Winthrop University Hospital, Mineola, NY 11501, USA. Electronic address: mpeltier@winthrop.org.
authors.forename: M R
authors.initials: MR
authors.lastname: Peltier
authors.affiliation: Women and Children's Research Laboratory, Winthrop University Hospital, Mineola, NY 11501, USA; Department of Pediatrics, Winthrop University Hospital, Mineola, NY 11501, USA. Electronic address: nhanna@winthrop.org.
authors.forename: N
authors.initials: N
authors.lastname: Hanna
mesh_terms: D000893:Anti-Inflammatory Agents; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000494:pharmacology*; D019332:Endothelin-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D010920:Placenta / Q000737:chemistry* / Q000187:drug effects*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D019332:Endothelin-1; D012333:RNA, Messenger; D002248:Carbon Monoxide
keywords: Carbon monoxide; Endothelin-1; Infection; Preterm birth