Nardhy Gomez-Lopez1,2,3, Roberto Romero2,4,5,6, Yi Xu1,2, Valeria Garcia-Flores1,2, Yaozhu Leng1,2, Bogdan Panaitescu1,2, Derek Miller1,2, Vikki M Abrahams7, Sonia S Hassan1,2. 1. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA. 2. Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD/NIH/DHHS, Bethesda, MD and Detroit, MI, USA. 3. Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI, USA. 4. Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA. 5. Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA. 6. Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA. 7. Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
Abstract
PROBLEM: Inflammasome activation requires two steps: priming and assembly of the multimeric complex. The second step includes assembly of the sensor molecule and adaptor protein ASC (an apoptosis-associated speck-like protein containing a CARD), which results in ASC speck formation and the recruitment of caspase (CASP)-1. Herein, we investigated whether there is inflammasome assembly in the chorioamniotic membranes and choriodecidual leukocytes from women who underwent spontaneous labor at term. METHOD OF STUDY: Using in situ proximity ligation assays, ASC/CASP-1 complexes were determined in the chorioamniotic membranes from women who delivered at term without labor or underwent spontaneous labor at term with or without acute histologic chorioamnionitis (n=10-11 each). Also, ASC speck formation was determined by flow cytometry in the choriodecidual leukocytes isolated from women who delivered at term with or without spontaneous labor (n=9-12 each). RESULTS: (i) ASC/CASP-1 complexes were detected in the chorioamniotic membranes; (ii) ASC/CASP-1 complexes were greater in the chorioamniotic membranes from women who underwent spontaneous labor at term than in those without labor; (iii) ASC/CASP-1 complexes were even more abundant in the chorioamniotic membranes from women who underwent spontaneous labor at term with acute histologic chorioamnionitis than in those without this placental lesion; (iv) ASC speck formation was detected in the choriodecidual leukocytes; and (v) ASC speck formation was greater in the choriodecidual leukocytes isolated from women who underwent spontaneous labor at term than in those without labor. CONCLUSION: There is inflammasome assembly in the chorioamniotic membranes and choriodecidual leukocytes during spontaneous labor at term. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.
PROBLEM: Inflammasome activation requires two steps: priming and assembly of the multimeric complex. The second step includes assembly of the sensor molecule and adaptor protein ASC (an apoptosis-associated speck-like protein containing a CARD), which results in ASC speck formation and the recruitment of caspase (CASP)-1. Herein, we investigated whether there is inflammasome assembly in the chorioamniotic membranes and choriodecidual leukocytes from women who underwent spontaneous labor at term. METHOD OF STUDY: Using in situ proximity ligation assays, ASC/CASP-1 complexes were determined in the chorioamniotic membranes from women who delivered at term without labor or underwent spontaneous labor at term with or without acute histologic chorioamnionitis (n=10-11 each). Also, ASC speck formation was determined by flow cytometry in the choriodecidual leukocytes isolated from women who delivered at term with or without spontaneous labor (n=9-12 each). RESULTS: (i) ASC/CASP-1 complexes were detected in the chorioamniotic membranes; (ii) ASC/CASP-1 complexes were greater in the chorioamniotic membranes from women who underwent spontaneous labor at term than in those without labor; (iii) ASC/CASP-1 complexes were even more abundant in the chorioamniotic membranes from women who underwent spontaneous labor at term with acute histologic chorioamnionitis than in those without this placental lesion; (iv) ASC speck formation was detected in the choriodecidual leukocytes; and (v) ASC speck formation was greater in the choriodecidual leukocytes isolated from women who underwent spontaneous labor at term than in those without labor. CONCLUSION: There is inflammasome assembly in the chorioamniotic membranes and choriodecidual leukocytes during spontaneous labor at term. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.
Entities:
Keywords:
ASC speck; acute chorioamnionitis; apoptosis-associated speck-like protein containing a CARD (ASC); caspase-1; interleukin-1 beta; intra-amniotic infection/inflammation
Authors: David P Sester; Sara J Thygesen; Vitaliya Sagulenko; Parimala R Vajjhala; Jasmyn A Cridland; Nazarii Vitak; Kaiwen W Chen; Geoffrey W Osborne; Kate Schroder; Katryn J Stacey Journal: J Immunol Date: 2014-11-17 Impact factor: 5.422
Authors: Pooja Mittal; Roberto Romero; Adi L Tarca; Juan Gonzalez; Sorin Draghici; Yi Xu; Zhong Dong; Chia-Ling Nhan-Chang; Tinnakorn Chaiworapongsa; Stephen Lye; Juan Pedro Kusanovic; Leonard Lipovich; Shali Mazaki-Tovi; Sonia S Hassan; Sam Mesiano; Chong Jai Kim Journal: J Perinat Med Date: 2010-07-14 Impact factor: 1.901
Authors: Y Gu; K Kuida; H Tsutsui; G Ku; K Hsiao; M A Fleming; N Hayashi; K Higashino; H Okamura; K Nakanishi; M Kurimoto; T Tanimoto; R A Flavell; V Sato; M W Harding; D J Livingston; M S Su Journal: Science Date: 1997-01-10 Impact factor: 47.728
Authors: R Romero; M Mazor; F Brandt; W Sepulveda; C Avila; D B Cotton; C A Dinarello Journal: Am J Reprod Immunol Date: 1992 Apr-May Impact factor: 3.886
Authors: Emily E Hadley; Samantha Sheller-Miller; George Saade; Carlos Salomon; Sam Mesiano; Robert N Taylor; Brandie D Taylor; Ramkumar Menon Journal: Am J Obstet Gynecol Date: 2018-08-21 Impact factor: 8.661
Authors: Jerome F Strauss; Roberto Romero; Nardhy Gomez-Lopez; Hannah Haymond-Thornburg; Bhavi P Modi; Maria E Teves; Laurel N Pearson; Timothy P York; Harvey A Schenkein Journal: Am J Obstet Gynecol Date: 2017-12-14 Impact factor: 8.661