Prolactin selectively inhibits the LPS-induced chemokine secretion of human foetal membranes

Abstract

Background: Inflammation is a condition that jeopardizes the continuity of pregnancy because it increases the secretion of chemokines that favor the migration of leukocytes from maternal and fetal circulations to the cervix, placenta, and the chorioamniotic membranes. During pregnancy, the level of prolactin (PRL) in the amniotic fluid is high; there is evidence to suggest that PRL contributes to maintain a privileged immune environment in the amniotic cavity. We test the effect of prolactin on the secretion profile of chemokines in human fetal membranes.

Methods: Nine fetal membranes collected from healthy nonlabouring cesarean deliveries at term. We placed whole membrane explants in a two-chamber culture system. Choriodecidua and amniotic chambers were pretreated with 250, 500, 1000, or 4000 ng/ml of PRL for 24 h, then choriodecidua was cotreated with 500 ng/ml of lipopolysaccharide (LPS) and PRL for 24 h. We used ELISA to measure secreted levels of four chemokines (RANTES, monocyte chemoattractant protein 1 (MCP-1), MIP-1α, and IL-8) in both amnion and choriodecidua regions.

Results: In comparison with basal conditions, LPS treatment induced significantly higher secretion of RANTES, MCP-1, and MIP-1α, but not of IL-8. RANTES was mainly produced by choriodecidua and cotreatment with PRL significantly decreased its LPS-induced secretion. MCP-1 was primarily produced by the amnion and its secretion was only inhibited by 4000 ng/ml of PRL. Both membrane regions produced MIP-1α, which was significantly inhibited at 1000 and 4000 ng/ml PRL concentrations. IL-8 showed no significant changes regardless of PRL concentration.

Conclusion: PRL inhibits the differential secretion of proinflammatory chemokines by human fetal membranes.

Keywords:

• Chemokines
• chorioamniotic membranes
• choriodecidual infection
• inflammation
• prolactin

Authors’ contributions

BQR coordinated the collected samples. EPM, LBM, AOO collected samples and performed microbiological control. LBM, PFE cultured chorioamniotic explants and performed stimulations. PFE, IMH carried out the ELISA tests. RVS coordinated data collection and provided statistical analysis. GEG, CHR, IM, CI, and VZC participated in the design of the study, data analysis, and manuscript preparation.

Ethics approval and consent to participate

The Ethical and Research Committees of the INPer IER (protocol 212250-06161) and HGOLCA (protocol IMSS R-2017-785-013) in Mexico City, Mexico approved this study.

Availability of data and materials

All data generated or analyzed during this study are included in this published article (and its Supplementary information files).

Acknowledgments

PFE was supported by the UNAM Graduate Program: Posgrado en Ciencias Biológicas. We thank Advancing Research Worldwide for language editing and correction. The authors thank the participating women for donating their fetal membranes for research. Additionally, we thank Irma Elena Sosa González and Graciela Villeda Gabriel from the Infectology and Immunology Branch for providing all microbiology analyses. We thank Dr. Adalberto Parra-Covarruvias for his contribution in formulating the original hypothesis of this project and its possible clinical implications. We also thank Dr. Sebastián Carranza-Lira from Hospital de Ginecolgia-Obstetricia No. 4, Luis Castelazo Ayala (HGOLCA) for his constant support during the project registration and the collection of biological samples.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by the Instituto Nacional de Perinatología Isidro Espinosa de los Reyes [grant No. 3210-21205-01-14 to VZC] and by National Council of Science and Technology of Mexico (CONACyT) [grant No. CB2014-24162 to VZC].