PMID- 27632777 OWN - NLM STAT- MEDLINE DCOM- 20171030 LR - 20181113 IS - 1530-0447 (Electronic) IS - 0031-3998 (Print) IS - 0031-3998 (Linking) VI - 81 IP - 1-1 DP - 2017 Jan TI - Ureaplasma infection-mediated release of matrix metalloproteinase-9 and PGP: a novel mechanism of preterm rupture of membranes and chorioamnionitis. PG - 75-79 LID - 10.1038/pr.2016.176 [doi] AB - BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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. FAU - Lal, Charitharth V AU - Lal CV AD - Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama. FAU - Xu, Xin AU - Xu X AD - Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama. FAU - Jackson, Patricia AU - Jackson P AD - Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama. FAU - Atkinson, Thomas P AU - Atkinson TP AD - Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama. AD - Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama. FAU - Faye-Petersen, Ona M AU - Faye-Petersen OM AD - Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama. FAU - Kandasamy, Jegen AU - Kandasamy J AD - Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama. FAU - Waites, Ken AU - Waites K AD - Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama. FAU - Biggio, Joseph R AU - Biggio JR AD - Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama. FAU - Gaggar, Amit AU - Gaggar A AD - Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama. FAU - Ambalavanan, Namasivayam AU - Ambalavanan N AD - Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama. LA - eng GR - R01 HL092906/HL/NHLBI NIH HHS/United States GR - I01 BX001756/BX/BLRD VA/United States GR - R01 AI072577/AI/NIAID NIH HHS/United States GR - R01 HL102371/HL/NHLBI NIH HHS/United States GR - R01 HL129907/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20160915 PL - United States TA - Pediatr Res JT - Pediatric research JID - 0100714 RN - 0 (Mitochondrial Proteins) RN - 0 (Oligopeptides) RN - 0 (Peptide Fragments) RN - 0 (prolyl-glycyl-proline) RN - 9007-34-5 (Collagen) RN - 9DLQ4CIU6V (Proline) RN - EC 2.4.21.25 (PREP protein, human) RN - EC 3.4.21.- (Serine Endopeptidases) RN - EC 3.4.24.35 (MMP9 protein, human) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Amniotic Fluid/metabolism MH - Chorioamnionitis/*etiology/*metabolism MH - Collagen/metabolism MH - Female MH - Fetal Membranes, Premature Rupture/*etiology/*metabolism MH - Humans MH - Matrix Metalloproteinase 9/*metabolism MH - Mitochondrial Proteins/metabolism MH - Models, Biological MH - Oligopeptides/*metabolism MH - Peptide Fragments/metabolism MH - Pregnancy MH - Pregnancy Complications, Infectious/*metabolism MH - Proline/*analogs & derivatives/metabolism MH - Serine Endopeptidases/metabolism MH - Spectrometry, Mass, Electrospray Ionization MH - Tandem Mass Spectrometry MH - Ureaplasma Infections/*complications/*metabolism PMC - PMC5235960 MID - NIHMS816070 COIS- Conflicts of interest/Financial Disclosures: There are no conflicts of interest or financial disclosures (other than funding as stated above) for any of the authors. EDAT- 2016/10/27 06:00 MHDA- 2017/10/31 06:00 PMCR- 2017/03/15 CRDT- 2016/09/16 06:00 PHST- 2016/04/09 00:00 [received] PHST- 2016/07/07 00:00 [accepted] PHST- 2016/10/27 06:00 [pubmed] PHST- 2017/10/31 06:00 [medline] PHST- 2016/09/16 06:00 [entrez] PHST- 2017/03/15 00:00 [pmc-release] AID - pr2016176 [pii] AID - 10.1038/pr.2016.176 [doi] PST - ppublish SO - Pediatr Res. 2017 Jan;81(1-1):75-79. doi: 10.1038/pr.2016.176. Epub 2016 Sep 15.