title: Heat-killed Lactobacillus rhamnosus GG modulates urocortin and cytokine release in primary trophoblast cells.
abstract: A number of studies are showing that probiotic treatment induces an anti-inflammatory state. Intrauterine infection can lead to preterm delivery by modulating immune function and efforts to prevent this condition are ongoing nowadays. Lactobacillus rhamnosus GG (LGG) is a probiotic known to ameliorate inflammation by increasing local anti-inflammatory mediators in urinary and gastrointestinal tracts. The present study then analyzed the effect of heat-killed LGG over β-hCG, progesterone, interleukins (IL) 4 and 10, tumor necrosis factor-α (TNF-α), corticotropin releasing hormone (CRH) and urocortin (Ucn) release by primary trophoblast cells. Normal human term placentas (n = 6) were collected and purified trophoblast cells were incubated in the presence of LGG, lipopolysaccharide (LPS) or either LGG + LPS during 3 h, after which the target substances were quantified by ELISA and real-time PCR. LGG did not affect β-hCG, progesterone, or CRH secretion. Conversely, LGG increased IL-4 protein and mRNA expression (P < 0.05) while IL-10 and Ucn secretion were increased in a dose dependent manner and the highest dose of LGG increased significantly IL-10 mRNA (P < 0.05). LGG did not alter TNF-α, while LPS exposure increased TNF-α protein (P < 0.001) and mRNA expression (P < 0.01). Conversely, LGG treatment reversed LPS-induced TNF-α release at both protein (P < 0.01) and mRNA levels (P < 0.05) in a dose dependent fashion. In conclusion, LGG stimulates IL-4, IL-10 and Ucn expression and reverses LPS-induced TNF-α release from trophoblast cells, with no change in β-hCG or progesterone release, suggesting that this probiotic may play a role as an immunomodulatory agent in human placenta without altering basic trophoblast functions.
authors.affiliation: Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, S Maria alle Scotte, viale Bracci 53100 Siena, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Bloise
authors.forename: M
authors.initials: M
authors.lastname: Torricelli
authors.forename: R
authors.initials: R
authors.lastname: Novembri
authors.forename: L E
authors.initials: LE
authors.lastname: Borges
authors.forename: P
authors.initials: P
authors.lastname: Carrarelli
authors.forename: F M
authors.initials: FM
authors.lastname: Reis
authors.forename: F
authors.initials: F
authors.lastname: Petraglia
mesh_terms: D006063:Chorionic Gonadotropin / Q000276:immunology; D003346:Corticotropin-Releasing Hormone / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D052201:Lacticaseibacillus rhamnosus / Q000276:immunology*; D010920:Placenta / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D011247:Pregnancy; D019936:Probiotics / Q000494:pharmacology*; D011374:Progesterone / Q000276:immunology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000166:cytology / Q000276:immunology*; D054832:Urocortins / Q000235:genetics / Q000276:immunology*
chemical_list: D006063:Chorionic Gonadotropin; D016207:Cytokines; D054832:Urocortins; D011374:Progesterone; D012313:RNA; D003346:Corticotropin-Releasing Hormone