Bogdan Panaitescu1,2, Roberto Romero1,3,4,5, Nardhy Gomez-Lopez1,2,6, Yi Xu1,2, Yaozhu Leng1,2, Eli Maymon1,2,7, Percy Pacora1,2, Offer Erez1,2,7, Lami Yeo1,2, Sonia S Hassan1,2,8, Chaur-Dong Hsu2. 1. a Perinatology Research Branch, NICHD/NIH/DHHS , Detroit , MI , USA. 2. b Department of Obstetrics & Gynecology , Wayne State University School of Medicine , Detroit , MI , USA. 3. c Department of Obstetrics & Gynecology , University of Michigan , Ann Arbor , MI , USA. 4. d Department of Epidemiology & Biostatistics , Michigan State University , East Lansing , MI , USA. 5. e Center for Molecular Medicine & Genetics , Wayne State University , Detroit , MI , USA. 6. f Department of Immunology, Microbiology & Biochemistry , Wayne State University School of Medicine , Detroit , MI , USA. 7. g Department of Obstetrics and Gynecology , Soroka University Medical Center, School of Medicine, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beersheba , Israel. 8. h Department of Physiology , Wayne State University School of Medicine , Detroit , MI , USA.
Abstract
OBJECTIVE: Upon inflammasome activation, the adaptor protein of the inflammasome ASC (apoptosis-associated speck-like protein containing a CARD) forms intracellular specks, which can be released into the extracellular space. The objectives of this study were to investigate whether (1) extracellular ASC is present in the amniotic fluid of women who delivered at term; (2) amniotic fluid ASC concentrations are greater in women who underwent spontaneous labor at term than in those who delivered at term in the absence of labor; and (3) amniotic epithelial and mesenchymal cells can form intracellular ASC specks in vitro. METHODS: This retrospective cross-sectional study included amniotic fluid samples from 41 women who delivered at term in the absence of labor (n = 24) or underwent spontaneous labor at term (n = 17). Amniotic epithelial and mesenchymal cells were also isolated from the chorioamniotic membranes obtained from a separate group of women who delivered at term (n = 3), in which ASC speck formation was assessed by confocal microscopy. Monocytes from healthy individuals were used as positive controls for ASC speck formation (n = 3). RESULTS: (1) The adaptor protein of the inflammasome ASC is detectable in the amniotic fluid of women who delivered at term; (2) amniotic fluid ASC concentration was higher in women who underwent spontaneous labor at term than in those who delivered at term without labor; and (3) amniotic epithelial and mesenchymal cells are capable of forming ASC specks and/or filaments in vitro. CONCLUSION: Amniotic fluid ASC concentrations are increased in women who undergo spontaneous labor at term. Amniotic epithelial and mesenchymal cells are capable of forming ASC specks, suggesting that these cells are a source of extracellular ASC in the amniotic fluid. These findings provide in vivo evidence that there is inflammasome activation in the amniotic cavity during the physiological process of labor at term.
OBJECTIVE: Upon inflammasome activation, the adaptor protein of the inflammasome ASC (apoptosis-associated speck-like protein containing a CARD) forms intracellular specks, which can be released into the extracellular space. The objectives of this study were to investigate whether (1) extracellular ASC is present in the amniotic fluid of women who delivered at term; (2) amniotic fluid ASC concentrations are greater in women who underwent spontaneous labor at term than in those who delivered at term in the absence of labor; and (3) amniotic epithelial and mesenchymal cells can form intracellular ASC specks in vitro. METHODS: This retrospective cross-sectional study included amniotic fluid samples from 41 women who delivered at term in the absence of labor (n = 24) or underwent spontaneous labor at term (n = 17). Amniotic epithelial and mesenchymal cells were also isolated from the chorioamniotic membranes obtained from a separate group of women who delivered at term (n = 3), in which ASC speck formation was assessed by confocal microscopy. Monocytes from healthy individuals were used as positive controls for ASC speck formation (n = 3). RESULTS: (1) The adaptor protein of the inflammasome ASC is detectable in the amniotic fluid of women who delivered at term; (2) amniotic fluid ASC concentration was higher in women who underwent spontaneous labor at term than in those who delivered at term without labor; and (3) amniotic epithelial and mesenchymal cells are capable of forming ASC specks and/or filaments in vitro. CONCLUSION: Amniotic fluid ASC concentrations are increased in women who undergo spontaneous labor at term. Amniotic epithelial and mesenchymal cells are capable of forming ASC specks, suggesting that these cells are a source of extracellular ASC in the amniotic fluid. These findings provide in vivo evidence that there is inflammasome activation in the amniotic cavity during the physiological process of labor at term.
Entities:
Keywords:
ASC speck; Amnion; PYD and CARD Domain-Containing Protein (Pycard); amniotic fluid; apoptosis-associated speck-like protein containing a CARD (ASC); caspase-1; chorioamniotic membranes; chorion; cytokine; interleukin-18; interleukin-1beta; intra-amniotic inflammation; parturition; pattern recognition receptor (PRR); pregnancy; sterile inflammation
Authors: P J Sansonetti; A Phalipon; J Arondel; K Thirumalai; S Banerjee; S Akira; K Takeda; A Zychlinsky Journal: Immunity Date: 2000-05 Impact factor: 31.745
Authors: A J Thomson; J F Telfer; A Young; S Campbell; C J Stewart; I T Cameron; I A Greer; J E Norman Journal: Hum Reprod Date: 1999-01 Impact factor: 6.918