PloS one · 2025
Placental inflammation is increased in gestational diabetes mellitus: The role of inflammasome NLRP-3 and chemokine scavenger decoy receptor D6.
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Onori Marianna, Beneduce Giuliana, Colella Filomena, Lucchetti Donatella, Policola Caterina, Arena Vincenzo, Sannino Fabio, Petrecca Alessandro, Pitocco Dario, Pontecorvi Alfredo, Sgambato Alessandro, Scambia Giovanni, Di Simone Nicoletta, Ghi Tullio, Tersigni Chiara
Аннотация
BACKGROUND: Gestational diabetes mellitus is characterized by low-grade systemic inflammation. Placental inflammation in gestation diabetes mellitus has not been extensively investigated yet.
OBJECTIVES: Aims of this study were to analyze: a) serum levels of Th-1 cytokines and D6-specific chemokines in women with gestation diabetes mellitus, compared to normal pregnant women; b) placental expression of the inflammasome NLR family pyrin domain containing 3 (NLRP-3) and the chemokines scavenger decoy D6 receptor.
METHODS: Serum samples collected between 24 and 28 weeks of pregnancy from singleton pregnancies with gestational diabetes mellitus and gestational age-matched normal pregnant women were analyzed by bead-based multiplex assays for chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-C motif) ligand 4 (CCL4), interferon gamma (IFN-γ), C-C motif chemokine ligand 11 (CCL11) and tumor necrosis factor alpha (TNF-α) levels. Placental samples from GDM and controls were analysed by immunohistochemistry and multiplex spatial immunofluorescence for protein expression of NLR family pyrin domain containing 3 (NLRP-3), interleukin-1 beta (IL-1β) and chemokines scavenger decoy D6 receptor.
RESULTS: GDM women (n = 25) showed higher serum levels of CCL-2 (p < 0.01), CCL-4 (p < 0.05) and IFN-γ (p < 0.05) compared to controls (n = 25). Placental expression of NLRP-3 was significantly higher in GDM women (n = 10) compared to controls (n = 7; p < 0.05) while only a trend of increase of IL-1β and D6 expression was observed in GDM compared to normal placentas.
CONCLUSIONS: GDM is characterized by higher serum levels of pro-inflammatory cytokines with consistent over-expression of the inflammasome NLRP-3 in placental tissues compared to normal pregnancy.
OBJECTIVES: Aims of this study were to analyze: a) serum levels of Th-1 cytokines and D6-specific chemokines in women with gestation diabetes mellitus, compared to normal pregnant women; b) placental expression of the inflammasome NLR family pyrin domain containing 3 (NLRP-3) and the chemokines scavenger decoy D6 receptor.
METHODS: Serum samples collected between 24 and 28 weeks of pregnancy from singleton pregnancies with gestational diabetes mellitus and gestational age-matched normal pregnant women were analyzed by bead-based multiplex assays for chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-C motif) ligand 4 (CCL4), interferon gamma (IFN-γ), C-C motif chemokine ligand 11 (CCL11) and tumor necrosis factor alpha (TNF-α) levels. Placental samples from GDM and controls were analysed by immunohistochemistry and multiplex spatial immunofluorescence for protein expression of NLR family pyrin domain containing 3 (NLRP-3), interleukin-1 beta (IL-1β) and chemokines scavenger decoy D6 receptor.
RESULTS: GDM women (n = 25) showed higher serum levels of CCL-2 (p < 0.01), CCL-4 (p < 0.05) and IFN-γ (p < 0.05) compared to controls (n = 25). Placental expression of NLRP-3 was significantly higher in GDM women (n = 10) compared to controls (n = 7; p < 0.05) while only a trend of increase of IL-1β and D6 expression was observed in GDM compared to normal placentas.
CONCLUSIONS: GDM is characterized by higher serum levels of pro-inflammatory cytokines with consistent over-expression of the inflammasome NLRP-3 in placental tissues compared to normal pregnancy.