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A Role for the Inflammasome in Spontaneous Preterm Labor With Acute Histologic Chorioamnionitis

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Abstract

Inflammasomes are cytosolic multiprotein complexes that orchestrate inflammation in response to pathogens and endogenous danger signals. Herein, we determined whether the chorioamniotic membranes from women in spontaneous preterm labor with acute histologic chorioamnionitis (1) express major inflammasome components; (2) express caspase (CASP)-l and CASP-4 as well as their active forms; (3) exhibit apoptosis-associated speck-like protein containing a CARD (ASC)/CASP-1 complex formation; and (4) release the mature forms of interleukin (IL)-1β and IL-18. We utilized quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, immunoblotting, and immunohistochemistry to determine the messenger RNA (mRNA) and protein expression of major inflammasome components, nucleotide-binding oligomerization domain (NOD) proteins, and the pro- and mature/active forms of CASP-1, CASP-4, IL-1β and IL-18. The ASC/CASP-1 complex formation was determined using an in situ proximity ligation assay. When comparing the chorioamniotic membranes from women in spontaneous preterm labor with acute histologic chorioamnionitis to those without this placental lesion, we found that (1) the mRNA of NLR family pyrin domain-containing protein (NLRP)I, NLRP3, NLR family CARD domain-containing protein 4 (NLRC4), and NOD2 were higher; (2) the NLRP3 protein was increased; (3) the mRNA and active form (p10) of CASP-1 were greater; (4) the mRNA and active form of CASP-4 were increased; (5) the mRNA and mature form of IL-β (3 were higher; (6) the mature form of IL-18 was elevated; and (7) ASC/CASP-1 complex formation was increased. In conclusion, spontaneous preterm labor with acute histologic chorioamnionitis is characterized by an upregulation of NLRP3 and the active form of CASP-4, as well as increased ASC/CASP-1 complex formation, which may participate in the activation of CASP-1 and the maturation of IL-1β and IL-18 in the chorioamniotic membranes. These findings provide the first evidence that supports a role for the inflammasome in the pathological inflammation implicated in spontaneous preterm labor 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, 3990 John R, Box 4, Detroit, MI, 48201, USA

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

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

    Nardhy Gomez-Lopez MSc, PhD, Yi Xu PhD, Olesya Plazyo MSc, Ronald Unkel BSc, Yaozhu Leng MSc, Tinnakorn Chaiworapongsa MD, Bogdan Panaitescu MD, PhD, Zhong Dong PhD, Adi L. Tarca, 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, PhD

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

    Nandor Gabor Than MD, PhD

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

    Nandor Gabor Than MD, PhD

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

    Vikki M. Abrahams PhD

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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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  14. Sonia S. Hassan MD
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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 Preterm Labor With Acute Histologic Chorioamnionitis. Reprod. Sci. 24, 1382–1401 (2017). https://doi.org/10.1177/1933719116687656

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