title: A Role for the Inflammasome in Spontaneous Labor at Term with Acute Histologic Chorioamnionitis.
abstract: Inflammasomes are cytosolic signaling platforms that regulate the activation of caspase (CASP)-1, which induces the maturation of interleukin (IL)-1β and IL-18. Herein, we determined whether the chorioamniotic membranes from women in spontaneous labor at term with acute histologic chorioamnionitis express major inflammasome components and whether these changes are associated with the activation of CASP-1 and CASP-4 and the release of mature IL-1β and IL-18. When comparing the chorioamniotic membranes from women in spontaneous labor at term with acute histologic chorioamnionitis to those without this placental lesion, we found that (1) the messenger RNA (mRNA) abundance of NLR family pyrin domain containing 3 ( NLRP3), NLR family CARD domain containing 4 ( NLRC4), absent in melanoma 2 ( AIM2), and nucleotide binding oligomerization domain 2 ( NOD2) was higher; (2) the NLRP3 and NLRC4 protein quantities were increased; (3) the mRNA and protein expressions of CASP-1 and its active forms were greater; (4) CASP-4 was increased at the mRNA level only; (5) the mRNA and protein expressions of IL-1β and its mature form were higher; and (6) a modest increase in the total protein concentration and abundance of the mature form of IL-18 was observed. In vitro incubation of the chorioamniotic membranes with the CASP-1 inhibitor, VX765, decreased the release of endotoxin-induced IL-1β and IL-18 (2-fold) but not IL-6 or tumor necrosis factor α. In conclusion, spontaneous labor at term with acute histologic chorioamnionitis is characterized by an upregulation of inflammasome components which, in turn, may participate in the activation of CASP-1 and lead to the release of mature IL-1β by the chorioamniotic membranes. These results support a role for the inflammasome in the mechanisms responsible for spontaneous labor at term with acute histologic chorioamnionitis.
authors.affiliation: 1 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.|2 Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.|3 Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Nardhy
authors.initials: N
authors.lastname: Gomez-Lopez
authors.affiliation: 1 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.|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.
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.affiliation: 1 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.|2 Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: 1 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.|2 Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Olesya
authors.initials: O
authors.lastname: Plazyo
authors.affiliation: 1 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.|2 Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Unkel
authors.affiliation: 1 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.|7 Systems Biology of Reproduction Lendulet Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.|8 Maternity Private Department, Kutvolgyi Clinical Block, Semmelweis University, Budapest, Hungary.|9 First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
authors.forename: Nandor Gabor
authors.initials: NG
authors.lastname: Than
authors.affiliation: 1 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.|2 Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Piya
authors.initials: P
authors.lastname: Chaemsaithong
authors.affiliation: 1 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.|2 Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
authors.affiliation: 1 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.|2 Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Dong
authors.affiliation: 1 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.|2 Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Adi L
authors.initials: AL
authors.lastname: Tarca
authors.affiliation: 10 Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Vikki M
authors.initials: VM
authors.lastname: Abrahams
authors.affiliation: 1 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.|2 Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Lami
authors.initials: L
authors.lastname: Yeo
authors.affiliation: 1 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.|2 Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
mesh_terms: D000293:Adolescent; D000328:Adult; D000650:Amnion / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020170:Caspase 1 / Q000378:metabolism; D053471:Caspases, Initiator / Q000378:metabolism; D002821:Chorioamnionitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002823:Chorion / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004151:Dipeptides / Q000494:pharmacology; D005260:Female; D006801:Humans; D058847:Inflammasomes / Q000276:immunology* / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007743:Labor, Obstetric / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D047929:Term Birth / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult; D062366:para-Aminobenzoates / Q000494:pharmacology
chemical_list: D004151:Dipeptides; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D062366:para-Aminobenzoates; C520022:belnacasan; C093516:CASP4 protein, human; D053471:Caspases, Initiator; D020170:Caspase 1
keywords: caspase-1; caspase-4; cytokine; endotoxin; fetal inflammatory response; fever; funisitis; intra-amniotic infection; intra-amniotic inflammation; lipopolysaccharide; microbial invasion of the amniotic cavity (MIAC); neutrophil; parturition; pregnancy