Presentation Title

Blockade of Cervix Ripening in a Murine Model of Preterm Birth

Faculty Mentor

Steven M. Yellon PhD

Start Date

18-11-2017 2:15 PM

End Date

18-11-2017 3:15 PM

Location

BSC-Ursa Minor 108

Session

Poster 3

Type of Presentation

Poster

Subject Area

health_nutrition_clinical_science

Abstract

Granulocyte-macrophage colony stimulating factor (GM-CSF) is a cytokine that drives pro-inflammatory proliferation by macrophages. GM-CSF is produced by immune cells, endothelial cells, and fibroblasts in response to an inflammatory signal, such as bacterial infection, analogous to lipopolysaccharide (LPS) and recruits monocytes from the circulatory system to become mature macrophages (Mφs) after tissue infiltration. LPS induces preterm ripening of the cervix as defined by increased presence of macrophages and degradation of extracellular collagen in preparation for preterm birth. The present study tested the hypothesis that inhibiting GM-CSF blocks cervix ripening and prevents inflammation-induced preterm birth. In this study, mice were treated on embryonic day 17 (E17) with saline (0.1ml intrauterine, n=4), LPS (250 μg Escherichia coli, 055: B5, Sigma Chemical Co, St Louis, MO; n=4), LPS+GM-CSF antibody or LPS+IgG antibody (0.200mg retro-orbital injection from Bio X Cell, West Lebanon, NH; n=4). Within 6h of injection, all LPS and LPS+IgG -treated mice had delivered at least 1 pup whereas 3 of 4 LPS+GM-CSF -treated mice and all saline controls did not deliver. Compared to controls, cell nuclei density decreased in cervix of LPS-treated mice, an effect blocked by GM-CSF antibody treatment. The density of Mφs appeared to diminish in LPS+GM-CSF vs LPS group, though not significantly, due in part to variability and low numbers/group. Overall, these findings indicate that blocking GM-CSF-mediated Mφ functions may prevent inflammation-induced preterm birth. The therapeutic value to arrest Mφ activities associated with premature ripening of the cervix in women at risk for preterm birth may be a promising approach for future studies. Supported by NIH R01HD054931.

Summary of research results to be presented

At six hours after treatment and compared to saline controls, the density of cell nuclei had decreased in the cervix of mice in the LPS group, an effect that was blocked in 75% of mice by the GM-CSF antibody treatment (p

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Nov 18th, 2:15 PM Nov 18th, 3:15 PM

Blockade of Cervix Ripening in a Murine Model of Preterm Birth

BSC-Ursa Minor 108

Granulocyte-macrophage colony stimulating factor (GM-CSF) is a cytokine that drives pro-inflammatory proliferation by macrophages. GM-CSF is produced by immune cells, endothelial cells, and fibroblasts in response to an inflammatory signal, such as bacterial infection, analogous to lipopolysaccharide (LPS) and recruits monocytes from the circulatory system to become mature macrophages (Mφs) after tissue infiltration. LPS induces preterm ripening of the cervix as defined by increased presence of macrophages and degradation of extracellular collagen in preparation for preterm birth. The present study tested the hypothesis that inhibiting GM-CSF blocks cervix ripening and prevents inflammation-induced preterm birth. In this study, mice were treated on embryonic day 17 (E17) with saline (0.1ml intrauterine, n=4), LPS (250 μg Escherichia coli, 055: B5, Sigma Chemical Co, St Louis, MO; n=4), LPS+GM-CSF antibody or LPS+IgG antibody (0.200mg retro-orbital injection from Bio X Cell, West Lebanon, NH; n=4). Within 6h of injection, all LPS and LPS+IgG -treated mice had delivered at least 1 pup whereas 3 of 4 LPS+GM-CSF -treated mice and all saline controls did not deliver. Compared to controls, cell nuclei density decreased in cervix of LPS-treated mice, an effect blocked by GM-CSF antibody treatment. The density of Mφs appeared to diminish in LPS+GM-CSF vs LPS group, though not significantly, due in part to variability and low numbers/group. Overall, these findings indicate that blocking GM-CSF-mediated Mφ functions may prevent inflammation-induced preterm birth. The therapeutic value to arrest Mφ activities associated with premature ripening of the cervix in women at risk for preterm birth may be a promising approach for future studies. Supported by NIH R01HD054931.