title: Neutrophil recruitment and activation in decidua with intra-amniotic IL-1beta in the preterm rhesus macaque.
abstract: Chorioamnionitis, an infection/inflammation of the fetomaternal membranes, is frequently associated with preterm delivery. The mechanisms of inflammation in chorioamnionitis are poorly understood. We hypothesized that neutrophils recruited to the decidua would be the major producers of proinflammatory cytokines. We injected intra-amniotic (IA) interleukin 1beta (IL-1beta) at ∼80% gestation in rhesus macaque monkeys, Macaca mulatta, delivered the fetuses surgically 24 h or 72 h after IA injections, and investigated the role of immune cells in the chorion-amnion decidua. IA IL-1beta induced a robust infiltration of neutrophils and significant increases of proinflammatory cytokines in the chorioamnion decidua at 24 h after exposure, with a subsequent decrease at 72 h. Neutrophils in the decidua were the major source of tumor necrosis factor alpha (TNFalpha) and IL-8. Interestingly, IA IL-1beta also induced a significant increase in anti-inflammatory indoleamine 2,3-dioxygenase (IDO) expression in the decidua neutrophils. The frequency of regulatory T cells (Tregs) and FOXP3 mRNA expression in the decidua did not change after IA IL-1beta injection. Collectively, our data demonstrate that in this model of sterile chorioamnionitis, the decidua neutrophils cause the inflammation in the gestational tissues but may also act as regulators to dampen the inflammation. These results help to understand the contribution of neutrophils to the pathogenesis of chorioamnionitis-induced preterm labor.
authors.affiliation: Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Pietro
authors.initials: P
authors.lastname: Presicce
authors.affiliation: Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Paranthaman
authors.initials: P
authors.lastname: Senthamaraikannan
authors.affiliation: Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Manuel
authors.initials: M
authors.lastname: Alvarez
authors.affiliation: Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio Division of Immunobiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Cesar M
authors.initials: CM
authors.lastname: Rueda
authors.affiliation: Division of Immunobiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Monica
authors.initials: M
authors.lastname: Cappelletti
authors.affiliation: California National Primate Research Center, University of California Davis, Davis, California Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Miller
authors.affiliation: Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Jobe
authors.affiliation: Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio Division of Immunobiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Claire A
authors.initials: CA
authors.lastname: Chougnet
authors.affiliation: Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio suhas.kallapur@cchmc.org.
authors.forename: Suhas G
authors.initials: SG
authors.lastname: Kallapur
mesh_terms: D000818:Animals; D003656:Decidua / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism*; D008253:Macaca mulatta; D020556:Neutrophil Infiltration / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D047928:Premature Birth / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; D053583:Interleukin-1beta; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha
keywords: IDO; chorioamnionitis; decidua; indoleamine 2,3-dioxygenase; inflammation; neutrophils