Progesterone Elicits an Inhibitory Effect upon <scp>LPS</scp>‐Induced Innate Immune Response in Pre‐Labor Human Amniotic Epithelium

Flores-Espinosa, Pilar; Pineda-Torres, Montzerrat; Vega-Sánchez, Rodrigo; Estrada-Gutiérrez, Guadalupe; Espejel-Núñez, Aurora; Flores-Pliego, Arturo; Maida-Claros, Rolando; Paredes-Vivas, Yuriria; Morales-Méndez, Iyari; Sosa-González, Irma; Chávez-Mendoza, Angel; Zaga‐Clavellina, Veronica

doi:10.1111/aji.12163

Cited by 37 publications

(52 citation statements)

References 67 publications

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“…parvum in the amnion and chorion. Using concentration of P4 comparable to levels in amniotic fluid in the second half of pregnancy [57] and comparable with previous publications [55, 56], P4 did not significantly inhibit U . parvum- induced IL-8, COX-2 and PGE 2 expression in amnion cells.…”

Section: Discussionsupporting

confidence: 90%

“…Mechanistically, it has been proposed to attenuate inflammatory responses in the cascade of events leading to adverse pregnancy outcomes. Previously, it had been shown that P4 elicits an inhibitory effect upon lipopolysaccharide (LPS)-induced innate immune response including tissue necrosis factor α (TNF-α) and IL-6 but not IL-8 in pre-labor human amniotic epithelium [55]. Another study found that progesterone represses IL-1β-induced IL-8 and COX-2 expression in human amnion epithelial cells [56].…”

Section: Discussionmentioning

confidence: 99%

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The Role of Progesterone and a Novel Progesterone Receptor, Progesterone Receptor Membrane Component 1, in the Inflammatory Response of Fetal Membranes to Ureaplasma parvum Infection

et al. 2016

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Ureaplasma parvum (U. parvum) is gaining recognition as an important pathogen for chorioamnionitis and preterm premature rupture of membranes. We aimed to investigate the roles of progesterone (P4) and a novel progesterone receptor, progesterone receptor membrane component 1 (PGRMC1), in the response of fetal membranes to U. parvum. Fetal membrane cells (amnion, chorion and decidua) were isolated and confirmed to be free of Mycoplasmataceae. Cells were treated with U. parvum (5x106 CFU), and adherence was quantified by qPCR. Amnion and chorion cells were transfected with scrambled siRNA or validated PGRMC1 siRNA for 72h. Cells were then treated with U. parvum for 4h with or without pretreatment with P4 (10−7 M) or ethanol for 1h. Interleukin-8 (IL-8), matrix metalloproteinase 9 (MMP9) and cyclooxygenase (COX-2) mRNA expression were quantified by qRT-PCR. Culture medium was harvested and analyzed for IL-8 and prostaglandin (PGE2) secretion by ELISA and MMP9 activity by zymography. U. parvum had a mean adherence of 15.0±0.6%, 16.9± 3.7% and 4.7±0.3% in cultured amnion, chorion and decidua cells, respectively. Exposure to U. parvum elicited significant inflammatory responses including induction of IL-8, COX-2, PGE2 and MMP9. A possible role of PGRMC1 was identified in the inhibition of U. parvum-stimulated COX-2 and MMP9 mRNA expression in chorion cells and MMP9 activity in amnion cells. On the other hand, it might enhance the U. parvum-stimulated IL-8 protein secretion in amnion cells. P4, mediated through PGRMC1, significantly inhibited U. Parvum-induced MMP9 mRNA and COX-2 mRNA expression in chorion cells. P4 appeared to attenuate U. parvum induced IL-8 mRNA expression in chorion cells, but this P4 effect might not mediated through PGRMC1. In summary, U. parvum preferentially adheres to and induces inflammatory responses in chorion and amnion cells. P4 and PGRMC1 appear to differentially modulate the inflammatory responses induced by U. parvum among amnion and chorion cells.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

The Role of Progesterone and a Novel Progesterone Receptor, Progesterone Receptor Membrane Component 1, in the Inflammatory Response of Fetal Membranes to Ureaplasma parvum Infection

et al. 2016

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“…By mimicking a potential in vivo response to immune challenge, our measure of ex vivo IL-1β production may have potential to predict future risk for inflammatory early birth among African American women not yet experiencing signs and symptoms of labor. Women known to be at risk for early birth via the inflammatory pathway may reap particular benefit from preventive interventions with anti-inflammatory properties, including progesterone and omega-3 fatty acid supplementation (Alvarez-Curto & Milligan, 2016; Flores-Espinosa et al, 2014). Indeed, decades of research in early birth prevention have strongly suggested that one size does not fit all.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-1 Receptor Antagonist Polymorphism and Birth Timing

et al. 2017

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Background Timing of birth is a major determinant of newborn health. African American women are at increased risk for early birth, particularly via the inflammatory pathway. Variants of the IL1RN) gene, which encode the interleukin-1 receptor antagonist (IL-1Ra) protein, are implicated in early birth. The biological pathways linking these variables remain unclear. Evidence also suggests inflammatory pathways differ by race; however, studies among African American women are lacking. Objectives We assessed whether an IL1RN variant was associated with timing of birth among African American women and whether this relationship was mediated by lower anti-inflammatory IL-1Ra production or related to a decrease in inhibition of proinflammatory IL-1β production. Methods A candidate gene study using a prospective cohort design was used. We collected blood samples at 28–32 weeks gestation among African American women experiencing an uncomplicated pregnancy (N = 89). IL1RN SNP rs2637988 was genotyped and lipopolysaccharide-stimulated IL-1Ra and IL-1β production quantified. Medical record review determined timing of birth. Results Women with GG genotype gave birth earlier than women with AA/AG genotypes (b* = 0.21, p = .04). There was no indirect effect of IL1RN SNP rs2637988 allele status on timing of birth through IL-1Ra production, as evidenced by a nonsignificant product of coefficients in mediational analyses (ab = .006, 95% CI [-0.05, 0.13]. Women with GG genotype demonstrated less inhibition of IL-1β production for a unit positive difference in IL-1Ra production than women with AA/AG genotypes (b* = 0.93, p = .03). Greater IL-1β production at 28–32 weeks of pregnancy was marginally associated with earlier birth (b* = 0.21, p = .05). Discussion Women with GG genotype may be at risk for earlier birth due to diminished IL-1β inhibition, allowing for initiation of a robust inflammatory response upon even mild immune challenge. Study of inflammatory contributions to early birth among African American women may be key to identifying potential prognostic markers of risk and targeted preventive interventions.

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“…It is worth noting that progesterone inhibits the innate immune response in pre-labor HAEC [53]. Thus, activation of such a response, including upregulation of HBD, may be beneficial for protection of both the mother and newborn during natural labor.…”

Section: Discussionmentioning

confidence: 99%

Human beta-defensin 1, 2 and 3 production by amniotic epithelial cells with respect to human papillomavirus (HPV) infection, HPV oncogenic potential and the mode of delivery

Szukiewicz

Alkhalayla

Pyźlak

et al. 2016

Microbial Pathogenesis

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Progesterone Elicits an Inhibitory Effect upon LPS‐Induced Innate Immune Response in Pre‐Labor Human Amniotic Epithelium

Cited by 37 publications

References 67 publications

The Role of Progesterone and a Novel Progesterone Receptor, Progesterone Receptor Membrane Component 1, in the Inflammatory Response of Fetal Membranes to Ureaplasma parvum Infection

The Role of Progesterone and a Novel Progesterone Receptor, Progesterone Receptor Membrane Component 1, in the Inflammatory Response of Fetal Membranes to Ureaplasma parvum Infection

Interleukin-1 Receptor Antagonist Polymorphism and Birth Timing

Human beta-defensin 1, 2 and 3 production by amniotic epithelial cells with respect to human papillomavirus (HPV) infection, HPV oncogenic potential and the mode of delivery

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