Roberto Romero1,2,3,4, Yi Xu1,5, Olesya Plazyo1,5, Piya Chaemsaithong1,5, Tinnakorn Chaiworapongsa1,5, Ronald Unkel1,5, Nandor Gabor Than1,6,7,8, Po Jen Chiang1, Zhong Dong1,5, Zhonghui Xu1,5, Adi L Tarca1,5, Vikki M Abrahams9, Sonia S Hassan1,5, Lami Yeo1,5, Nardhy Gomez-Lopez1,5,10. 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, University of Michigan, Ann Arbor, MI, USA. 3. Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA. 4. Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA. 5. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA. 6. Institute of Enzymology, Momentum Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary. 7. Maternity Private Department, Kutvolgyi Clinical Block, Semmelweis University, Budapest, Hungary. 8. First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. 9. Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. 10. Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI, USA.
Abstract
PROBLEM: Inflammasomes are signaling platforms that, upon sensing pathogens and sterile stressors, mediate the release of mature forms of interleukin (IL)-1β and IL-18. The aims of this study were to determine (i) the expression of major inflammasome components in the chorioamniotic membranes in spontaneous labor at term, (ii) whether there are changes in the inflammasome components associated with the activation of caspase-1 and caspase-4, and (iii) whether these events are associated with the release of the mature forms of IL-1β and IL-18. METHOD OF STUDY: Chorioamniotic membranes were collected from women at term with and without spontaneous labor. mRNA abundance and protein concentrations of inflammasome components, nucleotide-binding oligomerization domain-containing (NOD)1 and NOD2 proteins, caspase-1, caspase-4, IL-1β, and IL-18 were quantified by qRT-PCR (n = 28-29 each), ELISA (n = 10 each) or immunoblotting (n = 8 each), and immunohistochemistry (n = 10 each). Active caspase-1 and caspase-4, as well as mature IL-18, were determined by immunoblotting (n = 4 each), and pro- and mature forms of IL-1β were determined by ELISA (n = 4-7 each). RESULTS: Inflammasome components and NOD proteins were expressed in the chorioamniotic membranes obtained from women at term. The chorioamniotic membranes from women who underwent labor had (i) higher concentrations of NLRP3 (NOD-like receptor family, pyrin domain-containing protein 3) and NOD1 protein, (ii) greater immunoreactivity for caspase-1 and caspase-4, (iii) a greater quantity of the active form of caspase-1 (p20), and (iv) higher mRNA abundance and protein concentrations of pro- and mature IL-1β. However, mRNA abundance and protein concentrations of the mature form of IL-18 were not increased in tissues from women who underwent labor at term. CONCLUSIONS: Spontaneous labor at term is characterized by the expression of inflammasome components, which may participate in the activation of caspase-1 and lead to the cleavage and release of mature IL-1β by the chorioamniotic membranes. These results support the participation of the inflammasome in the mechanisms responsible for spontaneous parturition at term. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
PROBLEM: Inflammasomes are signaling platforms that, upon sensing pathogens and sterile stressors, mediate the release of mature forms of interleukin (IL)-1β and IL-18. The aims of this study were to determine (i) the expression of major inflammasome components in the chorioamniotic membranes in spontaneous labor at term, (ii) whether there are changes in the inflammasome components associated with the activation of caspase-1 and caspase-4, and (iii) whether these events are associated with the release of the mature forms of IL-1β and IL-18. METHOD OF STUDY: Chorioamniotic membranes were collected from women at term with and without spontaneous labor. mRNA abundance and protein concentrations of inflammasome components, nucleotide-binding oligomerization domain-containing (NOD)1 and NOD2 proteins, caspase-1, caspase-4, IL-1β, and IL-18 were quantified by qRT-PCR (n = 28-29 each), ELISA (n = 10 each) or immunoblotting (n = 8 each), and immunohistochemistry (n = 10 each). Active caspase-1 and caspase-4, as well as mature IL-18, were determined by immunoblotting (n = 4 each), and pro- and mature forms of IL-1β were determined by ELISA (n = 4-7 each). RESULTS: Inflammasome components and NOD proteins were expressed in the chorioamniotic membranes obtained from women at term. The chorioamniotic membranes from women who underwent labor had (i) higher concentrations of NLRP3 (NOD-like receptor family, pyrin domain-containing protein 3) and NOD1 protein, (ii) greater immunoreactivity for caspase-1 and caspase-4, (iii) a greater quantity of the active form of caspase-1 (p20), and (iv) higher mRNA abundance and protein concentrations of pro- and mature IL-1β. However, mRNA abundance and protein concentrations of the mature form of IL-18 were not increased in tissues from women who underwent labor at term. CONCLUSIONS: Spontaneous labor at term is characterized by the expression of inflammasome components, which may participate in the activation of caspase-1 and lead to the cleavage and release of mature IL-1β by the chorioamniotic membranes. These results support the participation of the inflammasome in the mechanisms responsible for spontaneous parturition at term. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
Authors: Chia-Ling Nhan-Chang; Roberto Romero; Adi L Tarca; Pooja Mittal; Juan Pedro Kusanovic; Offer Erez; Shali Mazaki-Tovi; Tinnakorn Chaiworapongsa; John Hotra; Nandor Gabor Than; Jung-Sun Kim; Sonia S Hassan; Chong Jai Kim Journal: Am J Obstet Gynecol Date: 2010-05 Impact factor: 8.661
Authors: A J Thomson; J F Telfer; A Young; S Campbell; C J Stewart; I T Cameron; I A Greer; J E Norman Journal: Hum Reprod Date: 1999-01 Impact factor: 6.918
Authors: K Takeda; H Tsutsui; T Yoshimoto; O Adachi; N Yoshida; T Kishimoto; H Okamura; K Nakanishi; S Akira Journal: Immunity Date: 1998-03 Impact factor: 31.745
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: Alexandra R Willcockson; Tulip Nandu; Cheuk-Lun Liu; Shanmugasundaram Nallasamy; W Lee Kraus; Mala Mahendroo Journal: Biol Reprod Date: 2018-03-01 Impact factor: 4.285
Authors: Jerome F Strauss; Roberto Romero; Nardhy Gomez-Lopez; Hannah Haymond-Thornburg; Bhavi P Modi; Maria E Teves; Laurel N Pearson; Timothy P York; Harvey A Schenkein Journal: Am J Obstet Gynecol Date: 2017-12-14 Impact factor: 8.661