(24) Vaginal putrescine attenuates microbe-mediated inflammation in the cervical epithelium

A Lactobacillus-deplete vaginal microbiota confers increased risk of preterm birth (PTB). Our group previously uncovered a role for vaginal polyamines in distinguishing individuals at greatest risk of PTB among those with similar microbiota-related risk. Putrescine is a polyamine primarily produced by anaerobes and abundant in a Lactobacillus-deplete microbiota. We have shown that vaginal metabolites, including select polyamines, can modify immune responses at the host-microbial interface. As immune perturbations can contribute to cervical remodeling preceding PTB, we hypothesized that putrescine promotes inflammation in the cervical epithelium as a mechanism underlying barrier disruption.


Study Design:

Ectocervical and endocervical epithelial cells were treated with putrescine (500-4000uM) for 24h. For microbial experiments, cells were treated with 10⁷ CFUs Gardnerella vaginalis (GV), an anaerobe prevalent in a Lactobacillus-deplete microbiota, in the presence or absence of putrescine. Inflammatory cytokines IL-8 and IL-1β were measured in cell culture media by ELISA.  One-way ANOVAs with Dunnet’s multiple comparisons tests were performed.



Results:

Putrescine has no effect on basal levels of IL-8 or IL-1β in ectocervical and endocervical cells (Fig. 1). Putrescine partially mitigates GV-induction of IL-8 in ectocervical and endocervical cells in a dose-dependent manner (Fig. 1A). Putrescine partially mitigates GV-induction of IL-1β in endocervical cells in a dose-dependent manner (Fig. 1B). While a similar trend was observed in ectocervical cells, putrescine did not significantly modify GV-induction of IL-1β (Fig. 1B).



Conclusion:

Contrary to our hypothesis, vaginal putrescine exerts an anti-inflammatory effect on the cervical epithelium. Our data suggest that this microbial metabolite may blunt host immune responses and promote tolerance of a Lactobacillus-deplete anaerobe-rich microbiota. The extent to which this molecular process may modify epithelial barrier stability, cervical remodeling, and PTB risk warrants future investigation. SMFM-AAOGF Award (KDG)