Effect of Lactobacillus rhamnosus GR-1 supernatant and fetal sex on lipopolysaccharide-induced cytokine and prostaglandin-regulating enzymes in human placental trophoblast cells: implications for treatment of bacterial vaginosis and prevention of preterm labor.
OBJECTIVE
The objective of the study was to determine the effect of fetal sex on the output of cytokines and prostaglandin-regulating enzymes in lipopolysaccharide (LPS) and probiotic lactobacilli-treated placental trophoblast cells.


METHODS
We examined the effect of LPS and Lactobacillus rhamnosus GR-1 supernatant in placental trophoblast cells on tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-10 using enzyme-linked immunosorbent assay and on prostaglandin-endoperoxide synthase 2 (PTGS2), 15-hydroxy prostaglandin dehydrogenase (PGDH), and toll-like receptor-4 (TLR-4) using Western blotting. Comparisons were performed using one-way analysis of variance and Student t test.


RESULTS
LPS increased the output of TNF-alpha, IL-10, and PTGS2 with a greater response in male placentae. L rhamnosus GR-1 supernatant inhibited the LPS-stimulated TNF-alpha and increased IL-10. It also up-regulated expression of PGDH in female placentae and partially reduced the LPS-stimulated PTGS2 in male placentae. There was no change in IL-1beta. Expression of TLR-4 was greater in placentae of male fetuses.


CONCLUSIONS
These findings suggest an underlying mechanism for the sex difference in the incidence of preterm birth and provide potential evidence for a therapeutic benefit of lactobacilli in reducing preterm labor.
Yeganegi
Maryam
M
Department of Physiology, University of Toronto, Toronto, ON, Canada.
Watson
Carole S
CS
Martins
Andrew
A
Kim
Sung O
SO
Reid
Gregor
G
Challis
John R G
JR
Bocking
Alan D
AD
D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D052201:Lacticaseibacillus rhamnosus / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D007752:Obstetric Labor, Premature / Q000517:prevention & control*; D011247:Pregnancy; D019936:Probiotics; D012737:Sex Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000201:enzymology / Q000382:microbiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016585:Vaginosis, Bacterial / Q000276:immunology / Q000378:metabolism / Q000628:therapy*
D016207:Cytokines; C508609:IL10 protein, human; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C082161:lipopolysaccharide A; D016753:Interleukin-10; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human