Block of Granulocyte-Macrophage Colony-Stimulating Factor Prevents Inflammation-Induced Preterm Birth in a Mouse Model for Parturition
| Autor: | Vladislav Kiveliyk, Vanessa Blanchard, Patricia A. Davis, Christopher Nold, Steven M. Yellon, Julie Stone, Kathleen O'Hara, Anthony T. Vella |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine medicine.medical_specialty Reproductive tract Reproductive medicine Inflammation Cervix Uteri Cell Line Andrology Mice 03 medical and health sciences 0302 clinical medicine Block (telecommunications) medicine Animals Humans RNA Messenger Cervix 030219 obstetrics & reproductive medicine business.industry Parturition Granulocyte-Macrophage Colony-Stimulating Factor Obstetrics and Gynecology Mesenchymal Stem Cells Original Articles Disease Models Animal 030104 developmental biology medicine.anatomical_structure Granulocyte macrophage colony-stimulating factor Embryology Premature Birth Female medicine.symptom business medicine.drug |
| Zdroj: | Reproductive Sciences. 26:551-559 |
| ISSN: | 1933-7205 1933-7191 |
| DOI: | 10.1177/1933719118804420 |
| Popis: | OBJECTIVE: A multitude of factors promotes inflammation in the reproductive tract leading to preterm birth. Macrophages peak in the cervix prior to birth and their numbers are increased by the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). We hypothesize GM-CSF is produced from multiple sites in the genital tract and is a key mediator in preterm birth. STUDY DESIGN: Ectocervical, endocervical, and amniotic fluid mesenchymal stem cells were treated with lipopolysaccharide (LPS), and the concentration and expression of GM-CSF was measured. Pregnant CD-1 mice on gestational day 17 received LPS and an intravenous injection of either anti-mouse GM-CSF or control antibody. After 6 hours, the preterm birth rate was recorded. RESULTS: Treatment with LPS increased the GM-CSF concentration and messenger RNA expression after 24 hours in all 3 cell lines (P < .01). Mice treated with LPS and the GM-CSF antibody had a preterm birth rate of 25%, compared to a 66.7% preterm birth rate in controls, within 6 hours (P < .05, χ(2)). Treatment with the anti-mouse GM-CSF antibody decreased the concentration of GM-CSF in the mouse serum (P < .01) but did not alter the number of macrophages or collagen content in the cervix. CONCLUSION: These studies demonstrate that GM-CSF is produced from multiple sites in the genital tract and that treatment with an antibody to GM-CSF prevents preterm birth. Curiously, the anti-mouse GM-CSF antibody did not decrease the number of macrophages in the cervix. Further research is needed to determine whether antibodies to GM-CSF can be utilized as a therapeutic agent to prevent preterm birth. |
| Databáze: | OpenAIRE |
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