Differential effect of LPS and IL-1β in term placental explants

Cyntia Duval, Marie Eve Brien, Virginie Gaudreault, Ines Boufaied, Bernadette Baker, Rebecca L. Jones, Sylvie Girard

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Inflammation is an important cause of placental dysfunction often associated with pregnancy complications. One well-known cause of inflammation is infection, through conserved “pathogen-associated molecular patterns” (PAMPs). Endogenous inducers of inflammation, known as “damage-associated molecular patterns” (DAMPs), have also been associated with pathological pregnancies and could contribute to the observed placental inflammation. Although both stimuli (i.e. PAMPs/DAMPs) can induce inflammation, they have yet to be studied together to compare their inflammatory effects on the placenta. Methods: We used a model of term placental explants to compare the effects of a classical PAMP, bacterial lipopolysaccharide (LPS), and a DAMP, the pro-inflammatory cytokine interleukin (IL)-1. Gene and protein expression of several cytokines were analysed by qPCR and ELISAs and immunohistochemistry performed to study placental resident immune cells and apoptosis. Results: LPS induced pro-inflammatory mediators (IL-6, IL-1β/α, TNF-α) whereas IL-1β induced only IL-6. Furthermore, LPS but not IL-1 exposure, led to elevated IL-10 and IL-1Ra secretion. Blocking the IL-1 signalling pathway abrogated the pro-inflammatory actions of LPS, whilst anti-inflammatory effects were preserved. The number of CD45 + immune cells was elevated in explants treated with LPS only. A subpopulation of CD45 + cells were positive for PCNA indicating proliferation of tissue resident macrophages. Discussion: We conclude that LPS, a classical PAMP, and IL-1, a DAMP, have shared and distinct actions with pro-inflammatory effects mediated through IL-1 but anti-inflammatory actions having a distinct pathway. Identification of an inflammatory mediator (i.e. IL-1) common to multiple stimuli could be a therapeutic target to preserve the placenta.

Original languageEnglish
Pages (from-to)9-15
Number of pages7
JournalPlacenta
Volume75
Early online date22 Nov 2018
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • DAMPs
  • Inflammation
  • Macrophages
  • PAMPs
  • Placenta

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

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