Human β-defensin-3 participates in intra-amniotic host defense in women with labor at term, spontaneous preterm labor and intact membranes, and preterm prelabor rupture of membranes

References

• Galask RP, Snyder IS. Antimicrobial factors in amniotic fluid. Am J Obstet Gynecol. 1970;106(1):59–65.
   PubMed Web of Science ®Google Scholar
• Miller J, Michel J, Bercovici B, et al. Studies on the antimicrobial activity of amniotic fluid. Am J Obstet Gynecol. 1976;125(2):212–214.
   PubMed Web of Science ®Google Scholar
• Tafari N, Ross SM, Naeye RL, et al. Failure of bacterial growth inhibition by amniotic fluid. Am J Obstet Gynecol. 1977;128(2):187–189.
   PubMed Web of Science ®Google Scholar
• Thadepalli H, Bach VT, Davidson EC Jr. Antimicrobial effect of amniotic fluid. Obstet Gynecol. 1978;52(2):198–204.
   PubMed Web of Science ®Google Scholar
• Thadepalli H, Gangopadhyay PK, Maidman JE. Amniotic fluid analysis for antimicrobial factors. Int J Gynecol Obstet. 1982;20(1):65–72.
   PubMed Web of Science ®Google Scholar
• Davis LE, McLaren LC, Stewart JA, et al. Immunological and microbiological studies of midtrimester amniotic fluid. Gynecol Obstet Invest. 1983;16(5):261–268.
   PubMed Web of Science ®Google Scholar
• Schmidt W. The amniotic fluid compartment: the fetal habitat. Adv Anat Embryol Cell Biol. 1992;127:1–100.
   PubMedGoogle Scholar
• Underwood MA, Gilbert WM, Sherman MP. Amniotic fluid: not just fetal urine anymore. J Perinatol. 2005;25(5):341–348.
   PubMedGoogle Scholar
• Dolin CD, Chan MK, Basch RS, et al. Human term amniotic fluid: a novel source of stem cells for regenerative medicine. Am J Obstet Gynecol. 2018;219(3):308–309.
   PubMed Web of Science ®Google Scholar
• Marquardt N, Ivarsson MA, Sundström E, et al. Fetal CD103+ IL-17-Producing Group 3 innate lymphoid cells represent the dominant lymphocyte subset in human amniotic fluid. J Immunol. 2016;197(8):3069–3075.
   PubMed Web of Science ®Google Scholar
• Gomez-Lopez N, Romero R, Xu Y, et al. The immunophenotype of amniotic fluid leukocytes in normal and complicated pregnancies. Am J Reprod Immunol. 2018;79(4):e12827.
   PubMed Web of Science ®Google Scholar
• Romero R, Brody DT, Oyarzun E, et al. Infection and labor. III. Interleukin-1: a signal for the onset of parturition. Am J Obstet Gynecol. 1989;160(5 Pt 1):1117–1123.
   PubMed Web of Science ®Google Scholar
• Romero R, Parvizi ST, Oyarzun E, et al. Amniotic fluid interleukin-1 in spontaneous labor at term. J Reprod Med. 1990;35(3):235–238.
   PubMed Web of Science ®Google Scholar
• Romero R, Mazor M, Brandt F, et al. Interleukin-1 alpha and interleukin-1 beta in preterm and term human parturition. Am J Reprod Immunol. 1992;27(3–4):117–123.
   PubMed Web of Science ®Google Scholar
• Hillier SL, Witkin SS, Krohn MA, et al. The relationship of amniotic fluid cytokines and preterm delivery, amniotic fluid infection, histologic chorioamnionitis, and chorioamnion infection. Obstet Gynecol. 1993;81(6):941–948.
   PubMed Web of Science ®Google Scholar
• Gomez R, Ghezzi F, Romero R, et al. Premature labor and intra-amniotic infection. Clinical aspects and role of the cytokines in diagnosis and pathophysiology. Clin Perinatol. 1995;22(2):281–342.
   PubMed Web of Science ®Google Scholar
• Hsu CD, Aversa K, Meaddough E, et al. Elevated amniotic fluid nitric oxide metabolites and cyclic guanosine 3',5'-monophosphate in pregnant women with intraamniotic infection. Am J Obstet Gynecol. 1997;177(4):793–796.
   PubMed Web of Science ®Google Scholar
• Yoon BH, Romero R, Jun JK, et al. Amniotic fluid cytokines (interleukin-6, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8) and the risk for the development of bronchopulmonary dysplasia. Am J Obstet Gynecol. 1997;177(4):825–830.
   PubMed Web of Science ®Google Scholar
• Hsu CD, Meaddough E, Hong SF, et al. Elevated amniotic fluid nitric oxide metabolites and interleukin-6 in intra-amniotic infection. J Soc Gynecol Investig. 1998;5(1):21–24.
   PubMedGoogle Scholar
• Hsu CD, Meaddough E, Aversa K, et al. Dual roles of amniotic fluid nitric oxide and prostaglandin E2 in preterm labor with intra-amniotic infection. Am J Perinatol. 1998;15(12):683–687.
   PubMed Web of Science ®Google Scholar
• Athayde N, Edwin SS, Romero R, et al. A role for matrix metalloproteinase-9 in spontaneous rupture of the fetal membranes. Am J Obstet Gynecol. 1998;179(5):1248–1253.
   PubMed Web of Science ®Google Scholar
• Hsu CD, Meaddough E, Aversa K, et al. Elevated amniotic fluid levels of leukemia inhibitory factor, interleukin 6, and interleukin 8 in intra-amniotic infection. Am J Obstet Gynecol. 1998;179(5):1267–1270.
   PubMed Web of Science ®Google Scholar
• Hsu CD, Meaddough E, Aversa K, et al. The role of amniotic fluid L-selectin, GRO-alpha, and interleukin-8 in the pathogenesis of intraamniotic infection. Am J Obstet Gynecol. 1998;178(3):428–432.
   PubMed Web of Science ®Google Scholar
• González-Bosquet E, Cerqueira MJ, Dominguez C, et al. Amniotic fluid glucose and cytokines values in the early diagnosis of amniotic infection in patients with preterm labor and intact membranes. J Matern Fetal Med. 1999;8(4):155–158.
   PubMedGoogle Scholar
• Hsu CD, Aversa KR, Lu LC, et al. Nitric oxide: a clinically important amniotic fluid marker to distinguish between intra-amniotic mycoplasma and non-mycoplasma infections. Am J Perinatol. 1999;16(4):161–166.
   PubMed Web of Science ®Google Scholar
• Lu LC, Hsu CD. Elevated amniotic fluid nucleosome levels in women with intra-amniotic infection. Obstet Gynecol. 1999;94(1):7–10.
   PubMed Web of Science ®Google Scholar
• Maymon E, Romero R, Pacora P, et al. Human neutrophil collagenase (matrix metalloproteinase 8) in parturition, premature rupture of the membranes, and intrauterine infection. Am J Obstet Gynecol. 2000;183(1):94–99.
   PubMed Web of Science ®Google Scholar
• Hsu CD, Aversa K, Meaddough E. The role of amniotic fluid interleukin-6, and cell adhesion molecules, intercellular adhesion molecule-1 and leukocyte adhesion molecule-1, in intra-amniotic infection. Am J Reprod Immunol. 2000;43(5):251–254.
   PubMed Web of Science ®Google Scholar
• Hsu CD, Hong SF, Harirah H, et al. Amniotic fluid soluble fas levels in intra-amniotic infection. Obstet Gynecol. 2000;95(5):667–670.
   PubMed Web of Science ®Google Scholar
• Maymon E, Romero R, Chaiworapongsa T, et al. Value of amniotic fluid neutrophil collagenase concentrations in preterm premature rupture of membranes. Am J Obstet Gynecol. 2001;185(5):1143–1148.
   PubMed Web of Science ®Google Scholar
• Angus SR, Segel SY, Hsu CD, et al. Amniotic fluid matrix metalloproteinase-8 indicates intra-amniotic infection. Am J Obstet Gynecol. 2001;185(5):1232–1238.
   PubMed Web of Science ®Google Scholar
• Maymon E, Romero R, Chaiworapongsa T, et al. Amniotic fluid matrix metalloproteinase-8 in preterm labor with intact membranes. Am J Obstet Gynecol. 2001;185(5):1149–1155.
   PubMed Web of Science ®Google Scholar
• Helmig BR, Romero R, Espinoza J, et al. Neutrophil elastase and secretory leukocyte protease inhibitor in prelabor rupture of membranes, parturition and intra-amniotic infection. J Matern Fetal Neonatal Med. 2002;12(4):237–246.
   PubMedGoogle Scholar
• Harirah H, Donia SE, Hsu CD. Amniotic fluid matrix metalloproteinase-9 and interleukin-6 in predicting intra-amniotic infection. Obstet Gynecol. 2002;99(1):80–84.
   PubMed Web of Science ®Google Scholar
• Romero R, Grivel JC, Tarca AL, et al. Evidence of perturbations of the cytokine network in preterm labor. Am J Obstet Gynecol. 2015;213(6):836.e1–836.e18.
   PubMed Web of Science ®Google Scholar
• Romero R, Chaemsaithong P, Korzeniewski SJ, et al. Clinical chorioamnionitis at term II: the intra-amniotic inflammatory response. J Perinat Med. 2016;44(1):5–22.
   PubMed Web of Science ®Google Scholar
• Musilova I, Andrys C, Drahosova M, et al. Amniotic fluid calreticulin in pregnancies complicated by the preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med. 2016;29(24):3921–3929.
   PubMed Web of Science ®Google Scholar
• Son GH, You YA, Kwon EJ, et al. Comparative analysis of midtrimester amniotic fluid cytokine levels to predict spontaneous very pre-term birth in patients with cervical insufficiency. Am J Reprod Immunol. 2016;75(2):155–161.
   PubMed Web of Science ®Google Scholar
• Martinez-Varea A, Romero R, Xu Y, et al. Clinical chorioamnionitis at term VII: the amniotic fluid cellular immune response. J Perinat Med. 2017;45(5):523–538.
   PubMed Web of Science ®Google Scholar
• Musilova I, Andrys C, Drahosova M, et al. Amniotic fluid cathepsin-G in pregnancies complicated by the preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med. 2017;30(17):2097–2104.
   PubMed Web of Science ®Google Scholar
• Chaemsaithong P, Romero R, Docheva N, et al. Comparison of rapid MMP-8 and interleukin-6 point-of-care tests to identify intra-amniotic inflammation/infection and impending preterm delivery in patients with preterm labor and intact membranes. J Matern Fetal Neonatal Med. 2018;31(2):228–244.
   PubMed Web of Science ®Google Scholar
• Gomez-Lopez N, Romero R, Panaitescu B, et al. Inflammasome activation during spontaneous preterm labor with intra-amniotic infection or sterile intra-amniotic inflammation. Am J Reprod Immunol. 2018;80(5):e13049.
   PubMed Web of Science ®Google Scholar
• Musilova I, Andrys C, Holeckova M, et al. Interleukin-6 measured using the automated electrochemiluminescence immunoassay method for the identification of intra-amniotic inflammation in preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med. 2018:1–131.
   PubMed Web of Science ®Google Scholar
• Gomez-Lopez N, Romero R, Garcia-Flores V, et al. Amniotic fluid neutrophils can phagocytize bacteria: a mechanism for microbial killing in the amniotic cavity. Am J Reprod Immunol. 2017;78(4).
   Web of Science ®Google Scholar
• Gomez-Lopez N, Romero R, Xu Y, et al. Neutrophil extracellular traps in the amniotic cavity of women with intra-amniotic infection: a new mechanism of host defense. Reprod Sci. 2017;24(8):1139–1153.
   PubMed Web of Science ®Google Scholar
• Gomez-Lopez N, Romero R, Leng Y, et al. Neutrophil extracellular traps in acute chorioamnionitis: a mechanism of host defense. Am J Reprod Immunol. 2017;77(3).
   Web of Science ®Google Scholar
• Schlievert P, Johnson W, Galask RP. Isolation of a low-molecular-weight antibacterial system from human amniotic fluid. Infect Immun. 1976;14(5):1156–1166.
   PubMed Web of Science ®Google Scholar
• Schlievert P, Johnson W, Galask RP. Amniotic fluid antibacterial mechanisms: newer concepts. Semin Perinatol. 1977;1(1):59–70.
   PubMed Web of Science ®Google Scholar
• Rueda R, Vargas ML, García-Pacheco M, et al. Detection of immunoregulatory lipid-like factors in human amniotic fluid. Am J Reprod Immunol. 1990;24(2):40–44.
   PubMed Web of Science ®Google Scholar
• Edwin SS, Romero RJ, Munoz H, et al. 5-Hydroxyeicosatetraenoic acid and human parturition. Prostaglandins. 1996;51(6):403–412.
   PubMed Web of Science ®Google Scholar
• Otsuki K, Yoda A, Toma Y, et al. Lactoferrin and interleukin-6 interaction in amniotic infection. Adv Exp Med Biol. 1998;443:267–271.
   PubMed Web of Science ®Google Scholar
• Petraglia F, Gomez R, Luisi S, et al. Increased midtrimester amniotic fluid activin A: a risk factor for subsequent fetal death. Am J Obstet Gynecol. 1999;180(1 Pt 1):194–197.
   PubMed Web of Science ®Google Scholar
• Pacora P, Maymon E, Gervasi MT, et al. Lactoferrin in intrauterine infection, human parturition, and rupture of fetal membranes. Am J Obstet Gynecol. 2000;183(4):904–910.
   PubMed Web of Science ®Google Scholar
• Espinoza J, Chaiworapongsa T, Romero R, et al. Antimicrobial peptides in amniotic fluid: defensins, calprotectin and bacterial/permeability-increasing protein in patients with microbial invasion of the amniotic cavity, intra-amniotic inflammation, preterm labor and premature rupture of membranes. J Matern Fetal Neonatal Med. 2003;13(1):2–21.
   PubMedGoogle Scholar
• Yoshio H, Tollin M, Gudmundsson GH, et al. Antimicrobial polypeptides of human vernix caseosa and amniotic fluid: implications for newborn innate defense. Pediatr Res. 2003;53(2):211–216.
   PubMed Web of Science ®Google Scholar
• Akinbi HT, Narendran V, Pass AK, et al. Host defense proteins in vernix caseosa and amniotic fluid. Am J Obstet Gynecol. 2004;191(6):2090–2096.
   PubMed Web of Science ®Google Scholar
• Bujold E, Romero R, Kusanovic JP, et al. Proteomic profiling of amniotic fluid in preterm labor using two-dimensional liquid separation and mass spectrometry. J Matern Fetal Neonatal Med. 2008;21(10):697–713.
   PubMed Web of Science ®Google Scholar
• Soto E, Espinoza J, Nien JK, et al. Human beta-defensin-2: a natural antimicrobial peptide present in amniotic fluid participates in the host response to microbial invasion of the amniotic cavity. J Matern Fetal Neonatal Med. 2007;20(1):15–22.
   PubMed Web of Science ®Google Scholar
• Iavazzo C, Tassis K, Gourgiotis D, et al. The role of human beta defensins 2 and 3 in the second trimester amniotic fluid in predicting preterm labor and premature rupture of membranes. Arch Gynecol Obstet. 2010;281(5):793–799.
   PubMed Web of Science ®Google Scholar
• Varrey A, Romero R, Panaitescu B, et al. Human beta-defensin-1: a natural antimicrobial peptide present in amniotic fluid that is increased in spontaneous preterm labor with intra-amniotic infection. Am J Reprod Immunol. 2018;80(4):e13031.
   PubMed Web of Science ®Google Scholar
• García JR, Jaumann F, Schulz S, et al. Identification of a novel, multifunctional beta-defensin (human beta-defensin 3) with specific antimicrobial activity. Its interaction with plasma membranes of Xenopus oocytes and the induction of macrophage chemoattraction. Cell Tissue Res. 2001;306(2):257–264.
   PubMed Web of Science ®Google Scholar
• Maisetta G, Batoni G, Esin S, et al. Activity of human beta-defensin 3 alone or combined with other antimicrobial agents against oral bacteria. Antimicrob Agents Chemother. 2003;47(10):3349–3351.
   PubMed Web of Science ®Google Scholar
• Semple CA, Rolfe M, Dorin JR. Duplication and selection in the evolution of primate beta-defensin genes. Genome Biol. 2003;4(5):R31.
   PubMed Web of Science ®Google Scholar
• Nagaoka I, Niyonsaba F, Tsutsumi-Ishii Y, et al. Evaluation of the effect of human beta-defensins on neutrophil apoptosis. Int Immunol. 2008;20(4):543–553.
   PubMed Web of Science ®Google Scholar
• Zanetti M, Gennaro R, Scocchi M, et al. Structure and biology of cathelicidins. Adv Exp Med Biol. 2000;479:203–218.
   PubMed Web of Science ®Google Scholar
• Lehrer RI, Ganz T. Defensins of vertebrate animals. Curr Opin Immunol. 2002;14(1):96–102.
   PubMed Web of Science ®Google Scholar
• Zanetti M. Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol. 2004;75(1):39–48.
   PubMed Web of Science ®Google Scholar
• Ganz T, Selsted ME, Szklarek D, et al. Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest. 1985;76(4):1427–1435.
   PubMed Web of Science ®Google Scholar
• Lichtenstein A. Mechanism of mammalian cell lysis mediated by peptide defensins. Evidence for an initial alteration of the plasma membrane. J Clin Invest. 1991;88(1):93–100.
   PubMed Web of Science ®Google Scholar
• Yang D, Biragyn A, Kwak LW, et al. Mammalian defensins in immunity: more than just microbicidal. Trends Immunol. 2002;23(6):291–296.
   PubMed Web of Science ®Google Scholar
• Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol. 2003;3(9):710–720.
   PubMed Web of Science ®Google Scholar
• Harwig SS, Park AS, Lehrer RI. Characterization of defensin precursors in mature human neutrophils. Blood. 1992;79(6):1532–1537.
   PubMed Web of Science ®Google Scholar
• Jones DE, Bevins CL. Paneth cells of the human small intestine express an antimicrobial peptide gene. J Biol Chem. 1992;267(32):23216–23225.
   PubMed Web of Science ®Google Scholar
• Schroeder BO, Ehmann D, Precht JC, et al. Paneth cell alpha-defensin 6 (HD-6) is an antimicrobial peptide. Mucosal Immunol. 2015;8(3):661–671.
   PubMed Web of Science ®Google Scholar
• Rice WG, Ganz T, Kinkade JM Jr, et al. Defensin-rich dense granules of human neutrophils. Blood. 1987;70(3):757–765.
   PubMed Web of Science ®Google Scholar
• Ganz T, Lehrer RI. Defensins. Curr Opin Immunol. 1994;6(4):584–589.
   PubMed Web of Science ®Google Scholar
• Zhao C, Wang I, Lehrer RI. Widespread expression of beta-defensin hBD-1 in human secretory glands and epithelial cells. FEBS Lett. 1996;396(2–3):319–322.
   PubMed Web of Science ®Google Scholar
• Mallow EB, Harris A, Salzman N, et al. Human enteric defensins. Gene structure and developmental expression. J Biol Chem. 1996;271(8):4038–4045.
   PubMed Web of Science ®Google Scholar
• Schneider JJ, Unholzer A, Schaller M, et al. Human defensins. J Mol Med. 2005;83(8):587–595.
   PubMed Web of Science ®Google Scholar
• Hein M, Valore EV, Helmig RB, et al. Antimicrobial factors in the cervical mucus plug. Am J Obstet Gynecol. 2002;187(1):137–144.
   PubMed Web of Science ®Google Scholar
• King AE, Fleming DC, Critchley HO, et al. Differential expression of the natural antimicrobials, beta-defensins 3 and 4, in human endometrium. J Reprod Immunol. 2003;59(1):1–16.
   PubMed Web of Science ®Google Scholar
• Ghartey JP, Carpenter C, Gialanella P, et al. Association of bactericidal activity of genital tract secretions with Escherichia coli colonization in pregnancy. Am J Obstet Gynecol. 2012;207(4):297.e1–297.e8.
   Web of Science ®Google Scholar
• Hughes BL, Dutt R, Raker C, et al. The impact of pregnancy on anti-HIV activity of cervicovaginal secretions. Am J Obstet Gynecol. 2016;215(6):748.e1–748.e12.
   Web of Science ®Google Scholar
• James CP, Bajaj-Elliott M, Abujaber R, et al. Human beta defensin (HBD) gene copy number affects HBD2 protein levels: impact on cervical bactericidal immunity in pregnancy. Eur J Hum Genet. 2018;26(3):434–439.
   PubMed Web of Science ®Google Scholar
• Garcia-Lopez G, Flores-Espinosa P, Zaga-Clavellina V. Tissue-specific human beta-defensins (HBD)1, HBD2, and HBD3 secretion from human extra-placental membranes stimulated with Escherichia coli. Reprod Biol Endocrinol. 2010;8:146.
   PubMed Web of Science ®Google Scholar
• King AE, Paltoo A, Kelly RW, et al. Expression of natural antimicrobials by human placenta and fetal membranes. Placenta. 2007;28(2–3):161–169.
   PubMed Web of Science ®Google Scholar
• Bai X, Tian T, Wang P, et al. Potential roles of placental human beta-defensin-3 and apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3G in prevention of intrauterine transmission of hepatitis B virus. J Med Virol. 2015;87(3):375–379.
   PubMed Web of Science ®Google Scholar
• Romero R, Mazor M, Wu YK, et al. Infection in the pathogenesis of preterm labor. Semin Perinatol. 1988;12(4):262–279.
   PubMed Web of Science ®Google Scholar
• Romero R, Mazor M. Infection and preterm labor. Clin Obstet Gynaecol. 1988;31(3):553–584.
   Web of Science ®Google Scholar
• Romero R, Sirtori M, Oyarzun E, et al. Infection and labor. V. Prevalence, microbiology, and clinical significance of intraamniotic infection in women with preterm labor and intact membranes. Am J Obstet Gynecol. 1989;161(3):817–824.
   PubMed Web of Science ®Google Scholar
• Romero R, Shamma F, Avila C, et al. Infection and labor. VI. Prevalence, microbiology, and clinical significance of intraamniotic infection in twin gestations with preterm labor. Am J Obstet Gynecol. 1990;163(3):757–761.
   PubMed Web of Science ®Google Scholar
• Romero R, Ghidini A, Mazor M, et al. Microbial invasion of the amniotic cavity in premature rupture of membranes. Clin Obstet Gynaecol. 1991;34(4):769–778.
   Web of Science ®Google Scholar
• Romero R, Mazor M, Morrotti R, et al. Infection and labor. VII. Microbial invasion of the amniotic cavity in spontaneous rupture of membranes at term. Am J Obstet Gynecol. 1992;166(1 Pt 1):129–133.
   PubMed Web of Science ®Google Scholar
• Romero R, Nores J, Mazor M, et al. Microbial invasion of the amniotic cavity during term labor. Prevalence and clinical significance. J Reprod Med. 1993;38(7):543–548.
   PubMed Web of Science ®Google Scholar
• Yoon BH, Romero R, Moon JB, et al. Clinical significance of intra-amniotic inflammation in patients with preterm labor and intact membranes. Am J Obstet Gynecol. 2001;185(5):1130–1136.
   PubMed Web of Science ®Google Scholar
• Seong HS, Lee SE, Kang JH, et al. The frequency of microbial invasion of the amniotic cavity and histologic chorioamnionitis in women at term with intact membranes in the presence or absence of labor. Am J Obstet Gynecol. 2008;199(4):375.e1–375.e5.
   Web of Science ®Google Scholar
• Romero R, Miranda J, Chaiworapongsa T, et al. A novel molecular microbiologic technique for the rapid diagnosis of microbial invasion of the amniotic cavity and intra-amniotic infection in preterm labor with intact membranes. Am J Reprod Immunol. 2014;71(4):330–358.
   PubMed Web of Science ®Google Scholar
• Romero R, Miranda J, Kusanovic JP, et al. Clinical chorioamnionitis at term I: microbiology of the amniotic cavity using cultivation and molecular techniques. J Perinat Med. 2015;43(1):19–36.
   PubMed Web of Science ®Google Scholar
• Musilova I, Andrys C, Drahosova M, et al. Amniotic fluid clusterin in pregnancies complicated by the preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med. 2017;30(21):2529–2537.
   PubMed Web of Science ®Google Scholar
• Romero R, Gomez-Lopez N, Kusanovic JP, et al. Clinical chorioamnionitis at term: new insights into the etiology, microbiology, and the fetal, maternal and amniotic cavity inflammatory responses. Nogyogyaszati Szuleszeti Tovabbkepzo Sz. 2018;20(3):103–112.
   PubMedGoogle Scholar
• Gervasi MT, Romero R, Bracalente G, et al. Midtrimester amniotic fluid concentrations of interleukin-6 and interferon-gamma-inducible protein-10: evidence for heterogeneity of intra-amniotic inflammation and associations with spontaneous early (<32 weeks) and late (>32 weeks) preterm delivery. J Perinat Med. 2012;40(4):329–343.
   PubMed Web of Science ®Google Scholar
• Romero R, Miranda J, Chaiworapongsa T, et al. Sterile intra-amniotic inflammation in asymptomatic patients with a sonographic short cervix: prevalence and clinical significance. J Matern Fetal Neonatal Med. 2014:1–17.
   PubMed Web of Science ®Google Scholar
• Romero R, Miranda J, Chaiworapongsa T, et al. Prevalence and clinical significance of sterile intra-amniotic inflammation in patients with preterm labor and intact membranes. Am J Reprod Immunol. 2014;72(5):458–474.
   PubMed Web of Science ®Google Scholar
• Chaemsaithong P, Romero R, Korzeniewski SJ, et al. A point of care test for the determination of amniotic fluid interleukin-6 and the chemokine CXCL-10/IP-10. J Matern Fetal Neonatal Med. 2015;28(13):1510–1519.
   PubMed Web of Science ®Google Scholar
• Romero R, Miranda J, Chaemsaithong P, et al. Sterile and microbial-associated intra-amniotic inflammation in preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med. 2015;28(12):1394–1409.
   PubMed Web of Science ®Google Scholar
• Romero R, Chaemsaithong P, Chaiyasit N, et al. CXCL10 and IL-6: markers of two different forms of intra-amniotic inflammation in preterm labor. Am J Reprod Immunol. 2017;78(1).
   Web of Science ®Google Scholar
• Gomez-Lopez N, Romero R, Maymon E, et al. Clinical chorioamnionitis at term IX: in vivo evidence of intra-amniotic inflammasome activation. J Perinat Med. 2018.
   PubMed Web of Science ®Google Scholar
• Romero R, Chaiworapongsa T, Alpay Savasan Z, et al. Damage-associated molecular patterns (DAMPs) in preterm labor with intact membranes and preterm PROM: a study of the alarmin HMGB1. J Matern Fetal Neonatal Med. 2011;24(12):1444–1455.
   PubMed Web of Science ®Google Scholar
• Combs CA, Gravett M, Garite TJ, et al. Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes. Am J Obstet Gynecol. 2014;210(2):125.e1–125.e15.
   PubMed Web of Science ®Google Scholar
• Chaemsaithong P, Romero R, Korzeniewski SJ, et al. A point of care test for interleukin-6 in amniotic fluid in preterm prelabor rupture of membranes: a step toward the early treatment of acute intra-amniotic inflammation/infection. J Matern Fetal Neonatal Med. 2016;29(3):360–367.
   PubMed Web of Science ®Google Scholar
• Yoneda N, Yoneda S, Niimi H, et al. Polymicrobial amniotic fluid infection with mycoplasma/Ureaplasma and other bacteria induces severe intra-amniotic inflammation associated with poor perinatal prognosis in preterm labor. Am J Reprod Immunol. 2016;75(2):112–125.
   PubMed Web of Science ®Google Scholar
• Chaemsaithong P, Romero R, Korzeniewski SJ, et al. A rapid interleukin-6 bedside test for the identification of intra-amniotic inflammation in preterm labor with intact membranes. J Matern Fetal Neonatal Med. 2016;29(3):349–359.
   PubMed Web of Science ®Google Scholar
• Musilova I, Bestvina T, Hudeckova M, et al. Vaginal fluid interleukin-6 concentrations as a point-of-care test is of value in women with preterm prelabor rupture of membranes. Am J Obstet Gynecol. 2016;215(5):619.e1–619.e12.
   Web of Science ®Google Scholar
• Park JY, Romero R, Lee J, et al. An elevated amniotic fluid prostaglandin F2alpha concentration is associated with intra-amniotic inflammation/infection, and clinical and histologic chorioamnionitis, as well as impending preterm delivery in patients with preterm labor and intact membranes. J Matern Fetal Neonatal Med. 2016;29(16):2563–2572.
   PubMed Web of Science ®Google Scholar
• Oh KJ, Kim SM, Hong JS, et al. Twenty-four percent of patients with clinical chorioamnionitis in preterm gestations have no evidence of either culture-proven intraamniotic infection or intraamniotic inflammation. Am J Obstet Gynecol. 2017;216(6):604.e1–604.e11.
   PubMed Web of Science ®Google Scholar
• Chaiyasit N, Romero R, Chaemsaithong P, et al. Clinical chorioamnionitis at term VIII: a rapid MMP-8 test for the identification of intra-amniotic inflammation. J Perinat Med. 2017;45(5):539–550.
   PubMed Web of Science ®Google Scholar
• Pacora P, Romero R, Erez O, et al. The diagnostic performance of the beta-glucan assay in the detection of intra-amniotic infection with Candida species. J Matern Fetal Neonatal Med. 2019;32(10):1703–1720.
   PubMed Web of Science ®Google Scholar
• Gomez-Lopez N, Romero R, Xu Y, et al. Are amniotic fluid neutrophils in women with intraamniotic infection and/or inflammation of fetal or maternal origin? Am J Obstet Gynecol. 2017;217(6):693.e1–693.e16.
   Web of Science ®Google Scholar
• Kusanovic JP, Romero R, Martinovic C, et al. Transabdominal collection of amniotic fluid “sludge” and identification of Candida albicans intra-amniotic infection. J Matern Fetal Neonatal Med. 2018;31(10):1279–1284.
   PubMed Web of Science ®Google Scholar
• Tricomi V, Hall JE, Bittar A, et al. Arborization test for the detection of ruptured fetal membranes. Clinical evaluation. Obstet Gynecol. 1966;27(2):275–279.
   PubMed Web of Science ®Google Scholar
• Friedman ML, McElin TW. Diagnosis of ruptured fetal membranes. Clinical study and review of the literature. Am J Obstet Gynecol. 1969;104(4):544–550.
   PubMed Web of Science ®Google Scholar
• Bennett SL, Cullen JB, Sherer DM, et al. The ferning and nitrazine tests of amniotic fluid between 12 and 41 weeks gestation. Am J Perinatol. 1993;10(2):101–104.
   PubMed Web of Science ®Google Scholar
• Tchirikov M, Zhumadilov ZS, Bapayeva G, et al. The effect of intraumbilical fetal nutrition via a subcutaneously implanted port system on amino acid concentration by severe IUGR human fetuses. J Perinat Med. 2017;45(2):227–236.
   PubMed Web of Science ®Google Scholar
• Romero R, Quintero R, Nores J, et al. Amniotic fluid white blood cell count: a rapid and simple test to diagnose microbial invasion of the amniotic cavity and predict preterm delivery. Am J Obstet Gynecol. 1991;165(4 Pt 1):821–830.
   PubMed Web of Science ®Google Scholar
• Romero R, Jimenez C, Lohda AK, et al. Amniotic fluid glucose concentration: a rapid and simple method for the detection of intraamniotic infection in preterm labor. Am J Obstet Gynecol. 1990;163(3):968–974.
   PubMed Web of Science ®Google Scholar
• Romero R, Emamian M, Quintero R, et al. The value and limitations of the Gram stain examination in the diagnosis of intraamniotic infection. Am J Obstet Gynecol. 1988;159(1):114–119.
   PubMed Web of Science ®Google Scholar
• Harder J, Bartels J, Christophers E, et al. Isolation and characterization of human beta -defensin-3, a novel human inducible peptide antibiotic. J Biol Chem. 2001;276(8):5707–5713.
   PubMed Web of Science ®Google Scholar
• Dhople V, Krukemeyer A, Ramamoorthy A. The human beta-defensin-3, an antibacterial peptide with multiple biological functions. Biochim Biophys Acta. 2006;1758(9):1499–1512.
   PubMed Web of Science ®Google Scholar
• Wu Z, Hoover DM, Yang D, et al. Engineering disulfide bridges to dissect antimicrobial and chemotactic activities of human beta-defensin 3. Proc Natl Acad Sci U S A. 2003;100(15):8880–8885.
   PubMed Web of Science ®Google Scholar
• Yang D, Chertov O, Bykovskaia SN, et al. Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science. 1999;286(5439):525–528.
   PubMed Web of Science ®Google Scholar
• Scott MG, Davidson DJ, Gold MR, et al. The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. J Immunol. 2002;169(7):3883–3891.
   PubMed Web of Science ®Google Scholar
• Bedran TB, Mayer MP, Spolidorio DP, et al. Synergistic anti-inflammatory activity of the antimicrobial peptides human beta-defensin-3 (hBD-3) and cathelicidin (LL-37) in a three-dimensional co-culture model of gingival epithelial cells and fibroblasts. PLoS One. 2014;9(9):e106766.
   PubMed Web of Science ®Google Scholar
• Romero R, Gotsch F, Pineles B, et al. Inflammation in pregnancy: its roles in reproductive physiology, obstetrical complications, and fetal injury. Nutr Rev. 2007;65(12 Pt 2):S194–S202.
   PubMed Web of Science ®Google Scholar
• Norman JE, Bollapragada S, Yuan M, et al. Inflammatory pathways in the mechanism of parturition. BMC Pregnancy Childbirth. 2007;7(Suppl 1):S7.
   PubMedGoogle Scholar
• Gomez-Lopez N, Guilbert LJ, Olson DM. Invasion of the leukocytes into the fetal-maternal interface during pregnancy. J Leukoc Biol. 2010;88(4):625–633.
   PubMed Web of Science ®Google Scholar
• Norwitz ER, Bonney EA, Snegovskikh VV, et al. Molecular regulation of parturition: the role of the decidual clock. Cold Spring Harb Perspect Med. 2015;5(11).
   PubMed Web of Science ®Google Scholar
• Herrera CA, Stoerker J, Carlquist J, et al. Cell-free DNA, inflammation, and the initiation of spontaneous term labor. Am J Obstet Gynecol. 2017;217(5):583.e1–583.e8.
   Web of Science ®Google Scholar
• Panaitescu B, Romero R, Gomez-Lopez N, et al. In vivo evidence of inflammasome activation during spontaneous labor at term. J Matern Fetal Neonatal Med. 2019;32(12):1978–1991.
   PubMed Web of Science ®Google Scholar
• Liggins CG. Cervical ripening as an inflammatory reaction. In: Elwood DA, Andersson ABM, editors. Cervix in pregnancy and labour. Edinburgh: Churchill Livingstone; 1981. p. 1–9.
   Google Scholar
• Bokström H, Brännström M, Alexandersson M, et al. Leukocyte subpopulations in the human uterine cervical stroma at early and term pregnancy. Hum Reprod. 1997;12(3):586–590.
   PubMed Web of Science ®Google Scholar
• Mackler AM, Iezza G, Akin MR, et al. Macrophage trafficking in the uterus and cervix precedes parturition in the mouse. Biol Reprod. 1999;61(4):879–883.
   PubMed Web of Science ®Google Scholar
• Young A, Thomson AJ, Ledingham M, et al. Immunolocalization of proinflammatory cytokines in myometrium, cervix, and fetal membranes during human parturition at term. Biol Reprod. 2002;66(2):445–449.
   PubMed Web of Science ®Google Scholar
• Kelly RW. Inflammatory mediators and cervical ripening. J Reprod Immunol. 2002;57(1–2):217–224.
   PubMed Web of Science ®Google Scholar
• Osman I, Young A, Ledingham MA, et al. Leukocyte density and pro-inflammatory cytokine expression in human fetal membranes, decidua, cervix and myometrium before and during labour at term. Mol Hum Reprod. 2003;9(1):41–45.
   PubMed Web of Science ®Google Scholar
• Yellon SM, Mackler AM, Kirby MA. The role of leukocyte traffic and activation in parturition. J Soc Gynecol Investig. 2003;10(6):323–338.
   PubMedGoogle Scholar
• Sakamoto Y, Moran P, Bulmer JN, et al. Macrophages and not granulocytes are involved in cervical ripening. J Reprod Immunol. 2005;66(2):161–173.
   PubMed Web of Science ®Google Scholar
• Yellon SM, Ebner CA, Sugimoto Y. Parturition and recruitment of macrophages in cervix of mice lacking the prostaglandin F receptor. Biol Reprod. 2008;78(3):438–444.
   PubMed Web of Science ®Google Scholar
• Timmons BC, Fairhurst AM, Mahendroo MS. Temporal changes in myeloid cells in the cervix during pregnancy and parturition. J Immunol. 2009;182(5):2700–2707.
   PubMed Web of Science ®Google Scholar
• Yellon SM, Oshiro BT, Chhaya TY, et al. Remodeling of the cervix and parturition in mice lacking the progesterone receptor B isoform. Biol Reprod. 2011;85(3):498–502.
   PubMed Web of Science ®Google Scholar
• Clyde LA, Lechuga TJ, Ebner CA, et al. Transection of the pelvic or vagus nerve forestalls ripening of the cervix and delays birth in rats. Biol Reprod. 2011;84(3):587–594.
   PubMed Web of Science ®Google Scholar
• Payne KJ, Clyde LA, Weldon AJ, et al. Residency and activation of myeloid cells during remodeling of the prepartum murine cervix. Biol Reprod. 2012;87(5):106.
   PubMed Web of Science ®Google Scholar
• Myers DA. The recruitment and activation of leukocytes into the immune cervix: further support that cervical remodeling involves an immune and inflammatory mechanism. Biol Reprod. 2012;87(5):107.
   PubMed Web of Science ®Google Scholar
• Furcron AE, Romero R, Plazyo O, et al. Vaginal progesterone, but not 17alpha-hydroxyprogesterone caproate, has antiinflammatory effects at the murine maternal-fetal interface. Am J Obstet Gynecol. 2015;213(846):e1–e19.
   PubMed Web of Science ®Google Scholar
• Willcockson AR, Nandu T, Liu CL, et al. Transcriptome signature identifies distinct cervical pathways induced in lipopolysaccharide-mediated preterm birth. Biol Reprod. 2018;98(3):408–421.
   PubMed Web of Science ®Google Scholar
• Thomson AJ, Telfer JF, Young A, et al. Leukocytes infiltrate the myometrium during human parturition: further evidence that labour is an inflammatory process. Hum Reprod. 1999;14(1):229–236.
   PubMed Web of Science ®Google Scholar
• Shynlova O, Tsui P, Dorogin A, et al. Monocyte chemoattractant protein-1 (CCL-2) integrates mechanical and endocrine signals that mediate term and preterm labor. J Immunol. 2008;181(2):1470–1479.
   PubMed Web of Science ®Google Scholar
• Shynlova O, Tsui P, Jaffer S, et al. Integration of endocrine and mechanical signals in the regulation of myometrial functions during pregnancy and labour. Eur J Obstet Gynecol Reprod Biol. 2009;144(Suppl 1):S2–S10.
   PubMed Web of Science ®Google Scholar
• Shynlova O, Lee YH, Srikhajon K, et al. Physiologic uterine inflammation and labor onset: integration of endocrine and mechanical signals. Reprod Sci. 2013;20(2):154–167.
   PubMed Web of Science ®Google Scholar
• Madaan A, Nadeau-Vallée M, Rivera JC, et al. Lactate produced during labor modulates uterine inflammation via GPR81 (HCA1). Am J Obstet Gynecol. 2017;216(1):60.e1–60.e17.
   Web of Science ®Google Scholar
• Lombardi A, Makieva S, Rinaldi SF, et al. Expression of matrix metalloproteinases in the mouse uterus and human myometrium during pregnancy, labor, and preterm labor. Reprod Sci. 2018;25(6):938–949.
   PubMed Web of Science ®Google Scholar
• Fidel PL Jr, Romero R, Ramirez M, et al. Interleukin-1 receptor antagonist (IL-1RA) production by human amnion, chorion, and decidua. Am J Reprod Immunol. 1994;32(1):1–7.
   PubMed Web of Science ®Google Scholar
• Keelan JA, Marvin KW, Sato TA, et al. Cytokine abundance in placental tissues: evidence of inflammatory activation in gestational membranes with term and preterm parturition. Am J Obstet Gynecol. 1999;181(6):1530–1536.
   PubMed Web of Science ®Google Scholar
• Lonergan M, Aponso D, Marvin KW, et al. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), TRAIL receptors, and the soluble receptor osteoprotegerin in human gestational membranes and amniotic fluid during pregnancy and labor at term and preterm. J Clin Endocrinol Metab. 2003;88(8):3835–3844.
   PubMed Web of Science ®Google Scholar
• Esplin MS, Peltier MR, Hamblin S, et al. Monocyte chemotactic protein-1 expression is increased in human gestational tissues during term and preterm labor. Placenta. 2005;26(8–9):661–671.
   PubMed Web of Science ®Google Scholar
• Gomez-Lopez N, Estrada-Gutierrez G, Jimenez-Zamudio L, et al. Fetal membranes exhibit selective leukocyte chemotaxic activity during human labor. J Reprod Immunol. 2009;80(1–2):122–131.
   PubMed Web of Science ®Google Scholar
• Gomez-Lopez N, Vadillo-Perez L, Hernandez-Carbajal A, et al. Specific inflammatory microenvironments in the zones of the fetal membranes at term delivery. Am J Obstet Gynecol. 2011;205(3):235.e15–235.e24.
   Web of Science ®Google Scholar
• Gomez-Lopez N, Vadillo-Perez L, Nessim S, et al. Choriodecidua and amnion exhibit selective leukocyte chemotaxis during term human labor. Am J Obstet Gynecol. 2011;204(4):364.e9–364.16.
   Web of Science ®Google Scholar
• Gomez-Lopez N, Tong WC, Arenas-Hernandez M, et al. Chemotactic activity of gestational tissues through late pregnancy, term labor, and RU486-induced preterm labor in Guinea pigs. Am J Reprod Immunol. 2015;73(4):341–352.
   PubMed Web of Science ®Google Scholar
• Gomez-Lopez N, Romero R, Xu Y, et al. Inflammasome assembly in the chorioamniotic membranes during spontaneous labor at term. Am J Reprod Immunol. 2017;77(5).
   Web of Science ®Google Scholar
• Romero R, Xu Y, Plazyo O, et al. A role for the inflammasome in spontaneous labor at term. Am J Reprod Immunol. 2018;79(6):e12440.
   PubMed Web of Science ®Google Scholar
• Hadley EE, Sheller-Miller S, Saade G, et al. Amnion epithelial cell-derived exosomes induce inflammatory changes in uterine cells. Am J Obstet Gynecol. 2018;219(5):478.e1–478.e21.
   Web of Science ®Google Scholar
• Vince GS, Starkey PM, Jackson MC, et al. Flow cytometric characterisation of cell populations in human pregnancy decidua and isolation of decidual macrophages. J Immunol Methods. 1990;132(2):181–189.
   PubMed Web of Science ®Google Scholar
• Keski-Nisula L, Aalto ML, Katila ML, et al. Intrauterine inflammation at term: a histopathologic study. Hum Pathol. 2000;31(7):841–846.
   PubMed Web of Science ®Google Scholar
• Hamilton S, Oomomian Y, Stephen G, et al. Macrophages infiltrate the human and rat decidua during term and preterm labor: evidence that decidual inflammation precedes labor. Biol Reprod. 2012;86(2):39.
   PubMed Web of Science ®Google Scholar
• Gomez-Lopez N, Vega-Sanchez R, Castillo-Castrejon M, et al. Evidence for a role for the adaptive immune response in human term parturition. Am J Reprod Immunol. 2013;69(3):212–230.
   PubMed Web of Science ®Google Scholar
• Hamilton SA, Tower CL, Jones RL. Identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour. PLoS One. 2013;8(2):e56946.
   PubMed Web of Science ®Google Scholar
• Gomez-Lopez N, StLouis D, Lehr MA, et al. Immune cells in term and preterm labor. Cell Mol Immunol. 2014;11(6):571–581.
   PubMed Web of Science ®Google Scholar
• Castillo-Castrejon M, Meraz-Cruz N, Gomez-Lopez N, et al. Choriodecidual cells from term human pregnancies show distinctive functional properties related to the induction of labor. Am J Reprod Immunol. 2014;71(1):86–93.
   PubMed Web of Science ®Google Scholar
• St Louis D, Romero R, Plazyo O, et al. Invariant NKT cell activation induces late preterm birth that is attenuated by rosiglitazone. J Immunol. 2016;196(3):1044–1059.
   PubMed Web of Science ®Google Scholar
• Xu Y, Romero R, Miller D, et al. An M1-like macrophage polarization in decidual tissue during spontaneous preterm labor that is attenuated by rosiglitazone treatment. J Immunol. 2016;196(6):2476–2491.
   PubMed Web of Science ®Google Scholar
• Arenas-Hernandez M, Gomez-Lopez N, Garcia-Flores V, et al. Choriodecidual leukocytes display a unique gene expression signature in spontaneous labor at term. Genes Immun. 2019;20(1):56–68.
   PubMed Web of Science ®Google Scholar
• Xu Y, Romero R, Miller D, et al. Innate lymphoid cells at the human maternal-fetal interface in spontaneous preterm labor. Am J Reprod Immunol. 2018;79(6):e12820.
   PubMed Web of Science ®Google Scholar
• Taylor K, Clarke DJ, McCullough B, et al. Analysis and separation of residues important for the chemoattractant and antimicrobial activities of beta-defensin 3. J Biol Chem. 2008;283(11):6631–6639.
   PubMed Web of Science ®Google Scholar
• Niyonsaba F, Ushio H, Nakano N, et al. Antimicrobial peptides human beta-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokines. J Invest Dermatol. 2007;127(3):594–604.
   PubMed Web of Science ®Google Scholar
• Hoover DM, Wu Z, Tucker K, et al. Antimicrobial characterization of human beta-defensin 3 derivatives. Antimicrob Agents Chemother. 2003;47(9):2804–2809.
   PubMed Web of Science ®Google Scholar
• Shelburne CE, Coulter WA, Olguin D, et al. Induction of {beta}-defensin resistance in the oral anaerobe Porphyromonas gingivalis. Antimicrob Agents Chemother. 2005;49(1):183–187.
   PubMed Web of Science ®Google Scholar
• Starner TD, Agerberth B, Gudmundsson GH, et al. Expression and activity of beta-defensins and LL-37 in the developing human lung. J Immunol. 2005;174(3):1608–1615.
   PubMed Web of Science ®Google Scholar
• Klüver E, Schulz-Maronde S, Scheid S, et al. Structure–activity relation of human beta-defensin 3: influence of disulfide bonds and cysteine substitution on antimicrobial activity and cytotoxicity. Biochemistry. 2005;44(28):9804–9816.
   PubMed Web of Science ®Google Scholar
• Zilbauer M, Dorrell N, Boughan PK, et al. Intestinal innate immunity to Campylobacter jejuni results in induction of bactericidal human beta-defensins 2 and 3. Infect Immun. 2005;73(11):7281–7289.
   PubMed Web of Science ®Google Scholar
• Lee SH, Jun HK, Lee HR, et al. Antibacterial and lipopolysaccharide (LPS)-neutralising activity of human cationic antimicrobial peptides against periodontopathogens. Int J Antimicrob Agents. 2010;35(2):138–145.
   PubMed Web of Science ®Google Scholar
• Otsuki K, Yoda A, Saito H, et al. Amniotic fluid lactoferrin in intrauterine infection. Placenta. 1999;20(2–3):175–179.
   PubMed Web of Science ®Google Scholar
• Friel LA, Romero R, Edwin S, et al. The calcium binding protein, S100B, is increased in the amniotic fluid of women with intra-amniotic infection/inflammation and preterm labor with intact or ruptured membranes. J Perinat Med. 2007;35(5):385–393.
   PubMed Web of Science ®Google Scholar
• Chaiworapongsa T, Erez O, Kusanovic JP, et al. Amniotic fluid heat shock protein 70 concentration in histologic chorioamnionitis, term and preterm parturition. J Matern Fetal Neonatal Med. 2008;21(7):449–461.
   PubMed Web of Science ®Google Scholar
• Romero R, Chaiworapongsa T, Savasan ZA, et al. Clinical chorioamnionitis is characterized by changes in the expression of the alarmin HMGB1 and one of its receptors, sRAGE. J Matern Fetal Neonatal Med. 2012;25(6):558–567.
   PubMed Web of Science ®Google Scholar
• Gomez-Lopez N, Romero R, Plazyo O, et al. Intra-amniotic administration of HMGB1 induces spontaneous preterm labor and birth. Am J Reprod Immunol. 2016;75(1):3–7.
   PubMed Web of Science ®Google Scholar
• Plazyo O, Romero R, Unkel R, et al. HMGB1 induces an inflammatory response in the chorioamniotic membranes that is partially mediated by the inflammasome. Biol Reprod. 2016;95(6):130.
   PubMed Web of Science ®Google Scholar
• Gomez-Lopez N, Romero R, Garcia-Flores V, et al. Inhibition of the NLRP3 inflammasome can prevent sterile intra-amniotic inflammation, preterm labor/birth and adverse neonatal outcomes. Biol Reprod. 2018. doi:10.1093/biolre/ioy264. [Epub ahead of print]
   Web of Science ®Google Scholar
• Tewary P, de la Rosa G, Sharma N, et al. Beta-Defensin 2 and 3 promote the uptake of self or CpG DNA, enhance IFN-alpha production by human plasmacytoid dendritic cells, and promote inflammation. J Immunol. 2013;191(2):865–874.
   PubMed Web of Science ®Google Scholar
• Krisanaprakornkit S, Weinberg A, Perez CN, et al. Expression of the peptide antibiotic human beta-defensin 1 in cultured gingival epithelial cells and gingival tissue. Infect Immun. 1998;66(9):4222–4228.
   PubMed Web of Science ®Google Scholar
• O’Neil DA, Porter EM, Elewaut D, et al. Expression and regulation of the human beta-defensins hBD-1 and hBD-2 in intestinal epithelium. J Immunol. 1999;163(12):6718–6724.
   PubMed Web of Science ®Google Scholar
• Harder J, Meyer-Hoffert U, Teran LM, et al. Mucoid Pseudomonas aeruginosa, TNF-alpha, and IL-1beta, but not IL-6, induce human beta-defensin-2 in respiratory epithelia. Am J Respir Cell Mol Biol. 2000;22(6):714–721.
   PubMed Web of Science ®Google Scholar
• Erez O, Romero R, Tarca AL, et al. Differential expression pattern of genes encoding for anti-microbial peptides in the fetal membranes of patients with spontaneous preterm labor and intact membranes and those with preterm prelabor rupture of the membranes. J Matern Fetal Neonatal Med. 2009;22(12):1103–1115.
   PubMed Web of Science ®Google Scholar