Preserved ex vivo inflammatory status in decidual cells from women with preterm labor and subclinical intrauterine infection.

PLoS One. 2012;7(8):e43605.

Castro-Leyva V, Espejel-Nuñez A, Barroso G, Zaga-Clavellina V, Flores-Pliego A, Morales-Mendez I, Giono-Cerezo S, Walsh SW, Estrada-Gutierrez G.

Department of Infectology, Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes, Mexico City, Mexico.

 

Abstract

OBJECTIVE: To compare the inflammatory response preserved ex vivo by decidual cells isolated from women who experienced preterm labor with and without subclinical intrauterine infection.

METHODS: Fetal membranes were obtained after cesarean section from 35 women who delivered before 37 weeks of gestation following spontaneous preterm labor, with no clinical evidence of intrauterine infection. Decidua was microbiologically tested and cultured. Concentrations of anti-inflammatory cytokines (IL-2, IL-4, IL-10), pro-inflammatory cytokines (IL-6, IL-8, IL-1β and TNF-α), and matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9) were measured in the supernatants using Bio-Plex, and prostaglandin E(2) (PGE(2)) was measured by enzyme immunoassay.

RESULTS: Subclinical infection was confirmed in 10 women (28.5%). Microorganisms isolated were Ureaplasma urealyticum (4), group B streptococci (3), Gardnerella vaginalis (1), and Escherichia coli (2). We found a significant increase of pro-inflammatory cytokines and a significant decrease of anti-inflammatory cytokines in supernatants from decidual cells obtained from women with preterm labor and subclinical intrauterine infection compared to women without infection. Secretion of MMP-1, MMP-8, MMP-9 and PGE(2) was significantly higher in infected women. Secretion of IL-8 by decidual cells from infected women persisted upon repeated in vitro culture passages.

CONCLUSIONS: Almost 30% of idiopathic preterm labor cases were associated with subclinical intrauterine infection, and decidual cells isolated from these cases preserved an ex vivo inflammatory status after in vivo bacterial exposure.

PMID: 22928002

 

Supplement

Despite the efforts of different research groups around the world, preterm birth remains the leading cause of perinatal morbidity and mortality. In our lab, we are particularly interested in the study of the molecular events that modulate infection-induced preterm birth.

During pregnancy, the reproductive tract is continuously exposed to commensal  and pathogen microorganisms, which can reach the intrauterine environment and trigger an inflammatory response. As decidual cells are the main resident cell type at the maternal-fetal interface, we consider that the immunological response elicited by these cells is a key event in the local inflammatory cascade that leads to preterm birth.

By combining classical microbiology and molecular biology with ex vivo cell culture, we were able to show in this work that decidual cells from women with subclinical intrauterine infection and preterm labor preserve their inflammatory status in culture. This finding provides a new insight into the immunological characterization of decidual cells, emerging as active players in the development of preterm labor.

Additional interesting data that we did not include in this paper show that different bacteria may induce a differential secretion of inflammatory biomarkers by decidual cells. For example, secretion of IL-8 by decidual cells isolated from women with preterm labor and group B streptococci (GBS)-associated subclinical intrauterine infection is increased 2-fold compared to cells isolated from cases with Ureaplasma urealyticum-associated subclinical infection (Figure 1). Ongoing work in our lab confirms this finding, so we hypothesize that decidual cells trigger alternative molecular pathways leading to preterm labor, as we demostrated before using a different in vitro model with intrauterine leukocytes (1).

Guadalupe Estrada-1Finally, in light of this work, we have developed new lines of research related to hormonal and epigenetic regulation of the inflammatory response in infected decidual cells, to elucidate the mechanisms by which these cells preserve the inflammatory status, even after several passages.

 

Reference:

1. Estrada GG, Gomez LN, Zaga CV, Giono CS, Espejel NA, Gonzalez JMA, Espino y Sosa S, Olson D, Vadillo OF. Interaction Between Pathogenic Bacteria and Intrauterine Leukocytes Triggers Alternative Molecular Signaling Cascades Leading to Labor in Women. Infect Immun 2010; 78: 4792-9

 

Contact

Guadalupe Estrada, Ph.D.

Researcher in Biomedical Sciences

Dept of Immunobiochemistry

Instituto Nacional de Perinatologia IER

Mexico City, Mexico

gpestrad@yahoo.es

Dr Estrada's Lab photo

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