TY - JOUR
T1 - Differential effect of LPS and IL-1β in term placental explants
AU - Duval, Cyntia
AU - Brien, Marie Eve
AU - Gaudreault, Virginie
AU - Boufaied, Ines
AU - Baker, Bernadette
AU - Jones, Rebecca L.
AU - Girard, Sylvie
N1 - Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2019/1
Y1 - 2019/1
N2 - 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.
AB - 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.
KW - DAMPs
KW - Inflammation
KW - Macrophages
KW - PAMPs
KW - Placenta
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U2 - 10.1016/j.placenta.2018.11.006
DO - 10.1016/j.placenta.2018.11.006
M3 - Article
C2 - 30712669
AN - SCOPUS:85057012814
SN - 0143-4004
VL - 75
SP - 9
EP - 15
JO - Placenta
JF - Placenta
ER -