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Lactobacillus rhamnosus GR-1-Induced IL-10 Production in Human Placental Trophoblast Cells Involves Activation of JAK/STAT and MAPK Pathways

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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.

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Authors and Affiliations

  1. Departments of Obstetrics/Gynaecology and Physiology, University of Toronto, Toronto, Ontario, Canada

    Maryam Yeganegi HBSc, PhD, Chiashan G. Leung HBSc, John R. G. Challis PhD & Alan D. Bocking MD

  2. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Room 1006, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada

    Maryam Yeganegi HBSc, PhD & Alan D. Bocking MD

  3. Departments of Microbiology, Immunology and Surgery, University of Western Ontario, Siebens and Drake Research Center, London, Ontario, Canada

    Andrew Martins BSc, Sung O. Kim PhD & Gregor Reid PhD

  4. Canadian Research and Development Centre for Probiotics, Lawson Health Research Institute, London, Ontario, Canada

    Gregor Reid PhD

Authors
  1. Maryam Yeganegi HBSc, PhD
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  2. Chiashan G. Leung HBSc
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  3. Andrew Martins BSc
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  4. Sung O. Kim PhD
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  5. Gregor Reid PhD
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  6. John R. G. Challis PhD
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  7. Alan D. Bocking MD
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Correspondence to Alan D. Bocking MD.

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Yeganegi, M., Leung, C.G., Martins, A. et al. Lactobacillus rhamnosus GR-1-Induced IL-10 Production in Human Placental Trophoblast Cells Involves Activation of JAK/STAT and MAPK Pathways. Reprod. Sci. 17, 1043–1051 (2010). https://doi.org/10.1177/1933719110377237

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