title: Lactobacillus rhamnosus GR-1-induced IL-10 production in human placental trophoblast cells involves activation of JAK/STAT and MAPK pathways.
abstract: Intrauterine infection/inflammation complicates 25% to 40% of preterm births (PTB). The human vagina is normally populated by Lactobacillus species, some of which upregulate interleukin 10 (IL-10) output in lipopolysaccharide (LPS)-treated human placental trophoblast cells. We hypothesize that a probiotic strain, L rhamnosus GR-1 exerts its anti-inflammatory effect through activation of the Janus Kinases/Signal Transducers and Activators of Transcription (JAK/STAT) and mitogen-activated protein kinase (MAPK) pathways. Placental trophoblasts from term healthy pregnancies were treated with LPS in the presence or absence of pretreatments with GR-1 supernatant and/or chemical inhibitors of the intracellular signaling pathways. Phosphorylation of STAT3 and p38 was measured by Western Blot analysis, and output of IL-10 was determined by enzyme-linked immunosorbent assay (ELISA). Phosphorylation of STAT-3 and p38 was upregulated by GR-1 supernatant alone or in combination with LPS, while IL-10 output was inhibited by both JAK and p38 inhibitors. These data provide an underlying intracellular mechanism for cytokine regulation in the human placenta by L rhamnosus GR-1 and potential prevention of infection/inflammation-mediated PTB.
authors.affiliation: Department of Obstetrics/Gynaecology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Maryam
authors.initials: M
authors.lastname: Yeganegi
authors.forename: Chiashan G
authors.initials: CG
authors.lastname: Leung
authors.forename: Andrew
authors.initials: A
authors.lastname: Martins
authors.forename: Sung O
authors.initials: SO
authors.lastname: Kim
authors.forename: Gregor
authors.initials: G
authors.lastname: Reid
authors.forename: John R G
authors.initials: JR
authors.lastname: Challis
authors.forename: Alan D
authors.initials: AD
authors.lastname: Bocking
mesh_terms: D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005260:Female; D006801:Humans; D056747:Immunomodulation; D016753:Interleukin-10 / Q000378:metabolism*; D053612:Janus Kinases / Q000378:metabolism*; D052201:Lacticaseibacillus rhamnosus / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D010920:Placenta / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D011247:Pregnancy; D050791:STAT Transcription Factors / Q000378:metabolism*; D014327:Trophoblasts / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D016585:Vaginosis, Bacterial / Q000276:immunology / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; C508609:IL10 protein, human; D050791:STAT Transcription Factors; D016753:Interleukin-10; D053612:Janus Kinases