Inflammasome activation during spontaneous preterm labor with intra-amniotic infection or sterile intra-amniotic inflammation

Nardhy Gomez-Lopez, Roberto Romero, Bogdan Panaitescu, Yaozhu Leng, Yi Xu, Adi L. Tarca, Jonathan Faro, Percy Pacora, Sonia S. Hassan, Chaur Dong Hsu

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Problem: The inflammasome is implicated in the mechanisms that lead to spontaneous preterm labor (PTL). However, whether there is inflammasome activation in the amniotic cavity of women with PTL and intra-amniotic infection (IAI) or sterile intra-amniotic inflammation (SIAI) is unknown. Method of study: Amniotic fluid samples were collected from women with PTL who delivered at term (n = 31) or preterm without IAI or SIAI (n = 35), with SIAI (n = 27), or with IAI (n = 17). As a readout of inflammasome activation, extracellular ASC (apoptosis-associated speck-like protein containing a CARD) was measured in amniotic fluid by ELISA and the expression of ASC, caspase-1, and interleukin (IL)-1β was detected in the chorioamniotic membranes by multiplex immunofluorescence. Acute inflammatory responses in amniotic fluid and the placenta were also evaluated. Results: (a) Amniotic fluid concentrations of ASC and IL-6 were higher in women with PTL and IAI or SIAI than in those who delivered preterm or at term without intra-amniotic inflammation; (b) amniotic fluid concentrations of ASC and IL-6 were lower in women with PTL and SIAI than in those with IAI; (c) there was a significant nonlinear correlation between ASC and IL-6 amniotic fluid concentrations; (d) the expression of inflammasome-related proteins (ASC, caspase-1, and IL-1β) in the chorioamniotic membranes was increased in women with PTL and IAI or SIAI than in those who delivered preterm or at term without intra-amniotic inflammation; (e) inflammasome activation in the chorioamniotic membranes was weaker in women with PTL and SIAI than in those with IAI; (f) women with PTL and IAI had elevated amniotic fluid white blood cell counts compared to those without this clinical condition; and (g) severe acute placental inflammatory lesions were observed in women with PTL and IAI and in a subset of women with PTL and SIAI. Conclusion: Inflammasome activation occurs in the settings of intra-amniotic infection and sterile intra-amniotic inflammation during spontaneous preterm labor.

Original languageEnglish (US)
Article numbere13049
JournalAmerican Journal of Reproductive Immunology
Volume80
Issue number5
DOIs
StatePublished - Nov 2018
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

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