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 - Funding Information:
Part of this work was supported by the Ste-Justine Hospital Foundation and by the Reseau Quebecois en Reproduction (RQR) (CD); the SickKids Foundation – Canadian Institute of Health Research (CIHR) – IHDCYH (SG), Fonds de Recherche Quebec Sante (FRQS) (SG), and the Medical Research Council (SG, RLJ). Funding sources were not involved in any part of the study design, analysis, interpretation and writing of this work. The authors have no competing interests to declare.
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
VL - 75
SP - 9
EP - 15
JO - Placenta
JF - Placenta
SN - 0143-4004
ER -