Nardhy Gomez-Lopez1,2,3, Roberto Romero1,4,5,6, Bogdan Panaitescu1,2, Yaozhu Leng1,2, Yi Xu1,2, Adi L Tarca1,2, Jonathan Faro1,2, Percy Pacora1,2, Sonia S Hassan1,2,7, Chaur-Dong Hsu2. 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, Bethesda, Maryland and Detroit, Michigan. 2. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan. 3. Department of Immunology, Microbiology and Biochemistry, Wayne State University School of Medicine, Detroit, Michigan. 4. Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan. 5. Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan. 6. Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan. 7. Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan.
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. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.
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. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.
Authors: Roberto Romero; Piya Chaemsaithong; Steven J Korzeniewski; Juan P Kusanovic; Nikolina Docheva; Alicia Martinez-Varea; Ahmed I Ahmed; Bo Hyun Yoon; Sonia S Hassan; Tinnakorn Chaiworapongsa; Lami Yeo Journal: J Perinat Med Date: 2016-01 Impact factor: 1.901
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
Authors: K Motomura; R Romero; V Garcia-Flores; Y Leng; Y Xu; J Galaz; R Slutsky; D Levenson; N Gomez-Lopez Journal: Mol Hum Reprod Date: 2020-09-01 Impact factor: 4.025