title: Ureaplasma infection-mediated release of matrix metalloproteinase-9 and PGP: a novel mechanism of preterm rupture of membranes and chorioamnionitis.
abstract: Premature rupture of membranes and preterm delivery are associated with Ureaplasma infection. We hypothesized that Ureaplasma induced extracellular collagen fragmentation results in production of the tripeptide PGP (proline-glycine-proline), a neutrophil chemoattractant. PGP release from collagen requires matrix metalloproteases (MMP-8/MMP-9) along with a serine protease, prolyl endopeptidase (PE).
  
  
  
  Ureaplasma culture negative amniotic fluid (indicated preterm birth, n = 8; spontaneous preterm birth, n = 8) and Ureaplasma positive amniotic fluid (spontaneous preterm birth, n = 8) were analyzed by electro-spray ionization-liquid chromatography tandem mass spectrometry for PGP, and for MMP-9 by zymography. PE was evaluated in lysates of U. parvum serovar 3 (Up3) and U. urealyticum serovar 10 (Uu10) by western blotting and activity assay.
  
  
  
  PGP and MMP-9 were increased in amniotic fluid from spontaneous preterm birth with positive Ureaplasma cultures, but not with indicated preterm birth or spontaneous preterm birth with negative Ureaplasma cultures. Human neutrophils cocultured with Ureaplasma strains showed increased MMP-9 activity. PE presence and activity were noted with both Ureaplasma strains.
  
  
  
  Ureaplasma spp. carry the protease necessary for PGP release, and PGP and MMP-9 are increased in amniotic fluid during Ureaplasma infection, suggesting Ureaplasma spp. induced collagen fragmentation contributes to preterm rupture of membranes and neutrophil influx causing chorioamnionitis.
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Charitharth V
authors.initials: CV
authors.lastname: Lal
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Patricia
authors.initials: P
authors.lastname: Jackson
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.|Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Atkinson
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Ona M
authors.initials: OM
authors.lastname: Faye-Petersen
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Jegen
authors.initials: J
authors.lastname: Kandasamy
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Ken
authors.initials: K
authors.lastname: Waites
authors.affiliation: Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Biggio
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Amit
authors.initials: A
authors.lastname: Gaggar
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Namasivayam
authors.initials: N
authors.lastname: Ambalavanan
mesh_terms: D000653:Amniotic Fluid / Q000378:metabolism; D002821:Chorioamnionitis / Q000209:etiology* / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000209:etiology* / Q000378:metabolism*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D008954:Models, Biological; D009842:Oligopeptides / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D016869:Ureaplasma Infections / Q000150:complications* / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; C113164:prolyl-glycyl-proline; D003094:Collagen; D011392:Proline; C514899:PREP protein, human; D012697:Serine Endopeptidases; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9