Identification of matrix metalloproteinase-9 in amniotic fluid and amniochorion in spontaneous labor and after experimental intrauterine infection or interleukin-1β infusion in pregnant rhesus monkeys

Vadillo-Ortega, Felipe; Sadowsky, Drew W.; Haluska, George J.; Hernández‐Guerrero, César; Guevara-Silva, Rebeca; Gravett, Michael G.; Novy, Miles J.

doi:10.1067/mob.2002.118916

Cited by 79 publications

(63 citation statements)

References 22 publications

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“…We found no changes in total matrix metalloproteinase activity in the amniotic fluid, which is consistent with both ex vivo and in vivo data suggesting that increased matrix metalloproteinase activity is localized within the membranes and fetus [34], [35]. In a pilot study of GBS choriodecidual infection in rhesus macaques, active MMP-9 only became elevated in the amniotic fluid of a single animal after a high dose GBS inoculum that resulted in preterm labor [36]. In early choriodecidual infection, local production and conversion to active enzyme within the fetal lungs may be a more likely mechanism of injury than direct exposure of the fetal lungs to matrix metalloproteinases in amniotic fluid.…”

Section: Discussionsupporting

confidence: 89%

Choriodecidual Group B Streptococcal Inoculation Induces Fetal Lung Injury without Intra-Amniotic Infection and Preterm Labor in Macaca nemestrina

et al. 2011

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BackgroundEarly events leading to intrauterine infection and fetal lung injury remain poorly defined, but may hold the key to preventing neonatal and adult chronic lung disease. Our objective was to establish a nonhuman primate model of an early stage of chorioamnionitis in order to determine the time course and mechanisms of fetal lung injury in utero.Methodology/Principal FindingsTen chronically catheterized pregnant monkeys (Macaca nemestrina) at 118–125 days gestation (term = 172 days) received one of two treatments: 1) choriodecidual and intra-amniotic saline (n = 5), or 2) choriodecidual inoculation of Group B Streptococcus (GBS) 1×106 colony forming units (n = 5). Cesarean section was performed regardless of labor 4 days after GBS or 7 days after saline infusion to collect fetal and placental tissues. Only two GBS animals developed early labor with no cervical change in the remaining animals. Despite uterine quiescence in most cases, blinded review found histopathological evidence of fetal lung injury in four GBS animals characterized by intra-alveolar neutrophils and interstitial thickening, which was absent in controls. Significant elevations of cytokines in amniotic fluid (TNF-α, IL-8, IL-1β, IL-6) and fetal plasma (IL-8) were detected in GBS animals and correlated with lung injury (p<0.05). Lung injury was not directly caused by GBS, because GBS was undetectable in amniotic fluid (∼10 samples tested/animal), maternal and fetal blood by culture and polymerase chain reaction. In only two cases was GBS cultured from the inoculation site in low numbers. Chorioamnionitis occurred in two GBS animals with lung injury, but two others with lung injury had normal placental histology.Conclusions/SignificanceA transient choriodecidual infection can induce cytokine production, which is associated with fetal lung injury without overt infection of amniotic fluid, chorioamnionitis or preterm labor. Fetal lung injury may, thus, occur silently without symptoms and before the onset of the fetal systemic inflammatory response syndrome.

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Section: Discussionsupporting

confidence: 89%

Choriodecidual Group B Streptococcal Inoculation Induces Fetal Lung Injury without Intra-Amniotic Infection and Preterm Labor in Macaca nemestrina

et al. 2011

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“…Data on the effect of pharmacological HDAC inhibition on NF-B seem contradictory, with some studies showing a potentiation Adam et al, 2003;Yeung et al, 2004) and others reporting an inhibition (Lü hrs et al, 2002;Takada et al, 2006) of NF-B activity. Several studies using the same HDACi compound used very different treatment protocols, with exposure of cells to HDACi ranging from 1 to 24 h. IL-1␤ activates NF-B, it is considered a master regulator of inflammation in diverse disease processes, its expression increases in the uterus as term approaches and in association with labor onset (Elliott et al, 2001;Mendelson and Condon, 2005), and administration of IL-1␤ can induce labor in the rhesus monkey (Vadillo-Ortega et al, 2002). We therefore tested both long-and short-term effects of the HDACi TSA on IL-1␤-induced NF-B activity in human myometrial cells.…”

Section: Resultsmentioning

confidence: 99%

Histone Deacetylase Inhibitors Exert Time-Dependent Effects on Nuclear Factor-κB but Consistently Suppress the Expression of Proinflammatory Genes in Human Myometrial Cells

Lindström

Mohan²,

Johnson³

et al. 2008

Mol Pharmacol

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Premature activation of the inflammatory processes that mediate human parturition leads to preterm birth, a major clinical problem associated with neonatal morbidity and mortality. Histone deacetylase inhibitors (HDACi) are currently in clinical trials for the treatment of inflammatory disorders. Recent evidence suggests that there may be a therapeutic use for HDACi in the management of preterm birth, with administration of HDACi to pregnant mice shown to delay delivery. Because NF-B is a key orchestrator of the inflammatory response and plays a pivotal role in parturition, it is important to understand how administration of HDACi might affect NF-B activity in human uterine tissues. We show here that the effects of HDACi on nuclear factor-B (NF-B) in human myometrial cells are time-dependent. Short-term exposure to HDACi enhanced interleukin (IL)-1␤-induced NF-B activity as a result of potentiating IB kinase (IKK)␤ activity, thereby leading to persistent turnover of IB␣/ proteins and prolonging NF-B phosphorylation, nuclear localization, and DNA binding. Conversely, longterm HDACi treatments resulted in repression of NF-B DNA binding. Nevertheless, both short-and long-term HDACi treatments inhibited the expression of four labor-associated proinflammatory genes (COX-2, IL-8, IL-6, and RANTES), and this was associated with repression of the proinflammatory transcription factor c-Jun. Together, our data indicate that HDACi exert anti-inflammatory effects in human myometrium and may thus be useful in achieving a myometrial gene expression profile that favors uterine quiescence. However, coadministration of an IKK␤ inhibitor may be both necessary and sufficient to circumvent potential induction of labor-associated pathways that could result from HDACi-induced augmentation of NF-B activity.During parturition, myometrium undergoes a transition from a state of quiescence to one of contractility, resulting in delivery of the neonate. Although the molecular mechanisms that underpin this transition are poorly understood, it is widely accepted that parturition is an inflammatory process, involving the up-regulation of multiple proinflammatory genes (Romero et al., 2006). Premature activation of uterine proinflammatory pathways can lead to preterm birth, a major clinical problem that occurs in 5 to 10% of pregnancies and is associated with 70 to 75% of neonatal morbidity/ mortality (Wen et al., 2004).Histone acetylation plays a major role in gene transcription, enabling the partial unraveling of local chromatin structure that is required to make the DNA accessible for binding by transcription factors and the basal transcription machinery (Li et al., 2004). Acetylation is reversible and reflects a dynamic balance between the activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Aberrant recruitment of HDACs to promoters and/or overexpression of HDACs are observed in cancer cells, and This work was supported by Tommy's Campaign. Article, publication date, and citation information can be foun...

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“…FM MMP-2 is constitutive and reportedly does not respond to cytokines or change with PPROM or labor (term or preterm) [Fortunato et al, 1999;Maymon et al, 2001;Xu et al, 2002]. In contrast, both active and latent forms of Bryant-Greenwood et al, 1995;Osmers et al, 1995;Athayde et al, 1999;Vadillo-Ortega et al, 2002). MMP-9 can also be induced in FM tissue with PGE 2 , PGF 2 , TNF and ROS (Buhimschi et al, 2000;Ulug et al, 2001;Arechavaleta-Velasco et al, 2002;Zaga et al, 2004).…”

Section: Term Fm Develops a Para-cervical "Weak Zone" Where Rupture Imentioning

confidence: 99%

Weakening and Rupture of Human Fetal Membranes – Biochemistry and Biomechanics

Rangaswamy¹,

Kumar²,

Moore³

et al. 2012

Preterm Birth - Mother and Child

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Identification of matrix metalloproteinase-9 in amniotic fluid and amniochorion in spontaneous labor and after experimental intrauterine infection or interleukin-1β infusion in pregnant rhesus monkeys

Cited by 79 publications

References 22 publications

Choriodecidual Group B Streptococcal Inoculation Induces Fetal Lung Injury without Intra-Amniotic Infection and Preterm Labor in Macaca nemestrina

Choriodecidual Group B Streptococcal Inoculation Induces Fetal Lung Injury without Intra-Amniotic Infection and Preterm Labor in Macaca nemestrina

Histone Deacetylase Inhibitors Exert Time-Dependent Effects on Nuclear Factor-κB but Consistently Suppress the Expression of Proinflammatory Genes in Human Myometrial Cells

Weakening and Rupture of Human Fetal Membranes – Biochemistry and Biomechanics

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