title: Alpha 1 antitrypsin activity is decreased in human amnion in premature rupture of the fetal membranes.
abstract: Preterm premature rupture of the membranes (PPROM) has been considered to be closely associated with chorioamnionitis. However, the detailed mechanism is not well understood. Alpha 1 antitrypsin (AAT) was reported to decrease in concentration in amniotic fluid obtained from patients with PPROM. However, the origin of AAT in amniotic fluid has not been clarified. In this study, we assessed the expression and localization of AAT in human amnion, as well as its biological activity in cases with PROM. Human amniotic epithelial (hAE) cells expressed AAT. After stimulation with oncostatin M (OSM), interleukin-6 (IL-6) or tumor necrotic factor alpha (TNF alpha), hAE cells increased the expression of AAT, while the expression of MMP9 was reduced by OSM and induced by TNF alpha. Oxidized AAT (inactivated form) was detected in the amnion with PPROM and TPROM, but not in specimens without PROM. Moreover, AAT activity was decreased in amnions from cases with PROM, regardless of gestational age. Thus, the results showed that AAT in the amnion may function as a protective shield at inflammatory sites, and not as it loses it inhibitory activity in cases with PROM, possibly by oxidation, suggesting that its imbalance contributes to PROM.
authors.affiliation: Department of Regenerative Medicine, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Izumi-Yoneda
authors.forename: Ayaka
authors.initials: A
authors.lastname: Toda
authors.forename: Motonori
authors.initials: M
authors.lastname: Okabe
authors.forename: Chika
authors.initials: C
authors.lastname: Koike
authors.forename: Seiji
authors.initials: S
authors.lastname: Takashima
authors.forename: Toshiko
authors.initials: T
authors.lastname: Yoshida
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Saito
authors.forename: Toshio
authors.initials: T
authors.lastname: Nikaido
mesh_terms: D000328:Adult; D000650:Amnion / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D053683:Oncostatin M / Q000494:pharmacology; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000378:metabolism*
chemical_list: D006131:Growth Inhibitors; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000515:alpha 1-Antitrypsin; D053683:Oncostatin M; D020780:Matrix Metalloproteinase 9