Nardhy Gomez-Lopez1,2,3, Roberto Romero1,4,5,6,7,8, Adi L Tarca1,2,9, Derek Miller1,2, Bogdan Panaitescu1,2, George Schwenkel1,2, Dereje W Gudicha1,2, Sonia S Hassan1,2,10, Percy Pacora1,2, Eunjung Jung1,2, Chaur-Dong Hsu1,2,10. 1. Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Detroit, MI, USA. 2. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA. 3. Department of Immunology, Microbiology and Biochemistry, 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. Detroit Medical Center, Detroit, MI, USA. 8. Department of Obstetrics and Gynecology, Florida International University, Miami, FL, USA. 9. Department of Computer Science, Wayne State University College of Engineering, Detroit, MI, USA. 10. Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA.
Abstract
PROBLEM: Pyroptosis, inflammatory programmed cell death, is initiated through the inflammasome and relies on the pore-forming actions of the effector molecule gasdermin D. Herein, we investigated whether gasdermin D is detectable in women with spontaneous preterm labor and sterile intra-amniotic inflammation or intra-amniotic infection. METHOD OF STUDY: Amniotic fluid samples (n = 124) from women with spontaneous preterm labor were subdivided into the following groups: (a) those who delivered at term (n = 32); and those who delivered preterm (b) without intra-amniotic inflammation (n = 41), (c) with sterile intra-amniotic inflammation (n = 32), or (d) with intra-amniotic infection (n = 19), based on amniotic fluid IL-6 concentrations and the microbiological status of amniotic fluid (culture and PCR/ESI-MS). Gasdermin D concentrations were measured using an ELISA kit. Multiplex immunofluorescence staining was also performed to determine the expression of gasdermin D, caspase-1, and interleukin-1β in the chorioamniotic membranes. Flow cytometry was used to detect pyroptosis (active caspase-1) in decidual cells from women with preterm labor and birth. RESULTS: (a) Gasdermin D was detected in the amniotic fluid and chorioamniotic membranes from women who underwent spontaneous preterm labor/birth with either sterile intra-amniotic inflammation or intra-amniotic infection, but was rarely detected in those without intra-amniotic inflammation. (b) Amniotic fluid concentrations of gasdermin D were higher in women with intra-amniotic infection than in those with sterile intra-amniotic inflammation, and its expression in the chorioamniotic membranes was associated with caspase-1 and IL-1β (inflammasome mediators). (c) Decidual stromal cells and leukocytes isolated from women with preterm labor and birth are capable of undergoing pyroptosis given their expression of active caspase-1. CONCLUSION: Pyroptosis can occur in the context of sterile intra-amniotic inflammation and intra-amniotic infection in patients with spontaneous preterm labor and birth.
PROBLEM: Pyroptosis, inflammatory programmed cell death, is initiated through the inflammasome and relies on the pore-forming actions of the effector molecule gasdermin D. Herein, we investigated whether gasdermin D is detectable in women with spontaneous preterm labor and sterile intra-amniotic inflammation or intra-amniotic infection. METHOD OF STUDY: Amniotic fluid samples (n = 124) from women with spontaneous preterm labor were subdivided into the following groups: (a) those who delivered at term (n = 32); and those who delivered preterm (b) without intra-amniotic inflammation (n = 41), (c) with sterile intra-amniotic inflammation (n = 32), or (d) with intra-amniotic infection (n = 19), based on amniotic fluid IL-6 concentrations and the microbiological status of amniotic fluid (culture and PCR/ESI-MS). Gasdermin D concentrations were measured using an ELISA kit. Multiplex immunofluorescence staining was also performed to determine the expression of gasdermin D, caspase-1, and interleukin-1β in the chorioamniotic membranes. Flow cytometry was used to detect pyroptosis (active caspase-1) in decidual cells from women with preterm labor and birth. RESULTS: (a) Gasdermin D was detected in the amniotic fluid and chorioamniotic membranes from women who underwent spontaneous preterm labor/birth with either sterile intra-amniotic inflammation or intra-amniotic infection, but was rarely detected in those without intra-amniotic inflammation. (b) Amniotic fluid concentrations of gasdermin D were higher in women with intra-amniotic infection than in those with sterile intra-amniotic inflammation, and its expression in the chorioamniotic membranes was associated with caspase-1 and IL-1β (inflammasome mediators). (c) Decidual stromal cells and leukocytes isolated from women with preterm labor and birth are capable of undergoing pyroptosis given their expression of active caspase-1. CONCLUSION: Pyroptosis can occur in the context of sterile intra-amniotic inflammation and intra-amniotic infection in patients with spontaneous preterm labor and birth.
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: Jose Galaz; Roberto Romero; Yi Xu; Derek Miller; Dustyn Levenson; Robert Para; Aneesha Varrey; Richard Hsu; Anna Tong; Sonia S Hassan; Chaur-Dong Hsu; Nardhy Gomez-Lopez Journal: J Perinat Med Date: 2020-09-25 Impact factor: 1.901