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A Role for the Inflammasome in Spontaneous Labor at Term with Acute Histologic Chorioamnionitis

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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 a. 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.

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Authors and Affiliations

  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, USA

    Nardhy Gomez-Lopez MSc, PhD, Roberto Romero MD, DMedSci, Yi Xu PhD, Olesya Plazyo PhD, Ronald Unkel BSc, Nandor Gabor Than MD, Piya Chaemsaithong MD, Tinnakorn Chaiworapongsa MD, Zhong Dong PhD, Adi L. Tarca PhD, Lami Yeo MD & Sonia S. Hassan MD

  2. Department of Obstetrics and Gynecology, Perinatology Research Branch, NICHD/NIH/DHHS, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    Nardhy Gomez-Lopez MSc, PhD, Yi Xu PhD, Olesya Plazyo PhD, Ronald Unkel BSc, Piya Chaemsaithong MD, Tinnakorn Chaiworapongsa MD, Zhong Dong PhD, Adi L. Tarca PhD, Lami Yeo MD & Sonia S. Hassan MD

  3. Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI, USA

    Nardhy Gomez-Lopez MSc, PhD

  4. Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA

    Roberto Romero MD, DMedSci

  5. Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA

    Roberto Romero MD, DMedSci

  6. Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA

    Roberto Romero MD, DMedSci

  7. Systems Biology of Reproduction Lendulet Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary

    Nandor Gabor Than MD

  8. Maternity Private Department, Kutvolgyi Clinical Block, Semmelweis University, Budapest, Hungary

    Nandor Gabor Than MD

  9. First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary

    Nandor Gabor Than MD

  10. Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA

    Vikki M. Abrahams PhD

  11. 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, Hutzel Women’s Hospital, 3990 John R, Box 4, Detroit, MI, 48201, USA

    Nardhy Gomez-Lopez MSc, PhD, Roberto Romero MD, DMedSci, Yi Xu PhD, Olesya Plazyo PhD, Ronald Unkel BSc, Nandor Gabor Than MD, Piya Chaemsaithong MD, Tinnakorn Chaiworapongsa MD, Zhong Dong PhD, Adi L. Tarca PhD, Lami Yeo MD & Sonia S. Hassan MD

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  1. Nardhy Gomez-Lopez MSc, PhD
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  2. Roberto Romero MD, DMedSci
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  3. Yi Xu PhD
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Corresponding authors

Correspondence to Nardhy Gomez-Lopez MSc, PhD or Roberto Romero MD, DMedSci.

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Gomez-Lopez, N., Romero, R., Xu, Y. et al. A Role for the Inflammasome in Spontaneous Labor at Term with Acute Histologic Chorioamnionitis. Reprod. Sci. 24, 934–953 (2017). https://doi.org/10.1177/1933719116675058

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