title: Intra-amniotic LPS modulates expression of antimicrobial peptides in the fetal sheep lung.
abstract: BACKGROUND
  Damage-associated molecular patterns (DAMPs) and antimicrobial peptides (AMPs) are components of pulmonary innate immunity and tissue repair. We hypothesized that DAMPs and AMPs would increase in response to fetal pulmonary inflammation caused by chorioamnionitis in a time-dependent manner.
  
  
  METHODS
  Fetal sheep were exposed to intra-amniotic saline or lipopolysaccharide (LPS) (10 mg) between 5 h and 15 d prior to preterm delivery at 125 ± 2 d. Lung tissue mRNAs for proinflammatory cytokines; AMPs: myeloid AMP-29 (MAP29), dodecapeptide, sheep β-defensin-1 (SBD1), and sheep β-defensin-2 (SBD2); and DAMPs: interleukin (IL)-1α, lactoferrin, heat-shock protein-70 (HSP70), high-mobility group box protein-B1 (HMGB1), and receptor for advanced glycation endproducts (RAGE) were measured by reverse-transcriptase quantitative polymerase chain reaction. Immunohistochemistry of DAMPs and in situ hybridization of AMPs was performed.
  
  
  RESULTS
  IL-1α, IL-1β, IL-6, IL-8, IL-10, MCP-1, and tumor necrosis factor (TNF)-α mRNA increased after LPS exposure. MAP29, dodecapeptide, SBD1, and SBD2 mRNA were suppressed at 24 h. MAP29 and dodecapeptide mRNA then increased at 8 d. Lactoferrin increased at 24 h. There were no changes for HMGB1, HSP70, or RAGE. MAP29 and dodecapeptide localized to alveolar cells, increased 8 d after exposure to LPS.
  
  
  CONCLUSIONS
  AMPs are initially suppressed in the fetal lung by LPS-induced chorioamnionitis. The late induction of MAP29 and dodecapeptide may be related to lung repair.
authors.affiliation: Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Augusto F
authors.initials: AF
authors.lastname: Schmidt
authors.affiliation: Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Paranthaman S
authors.identifier: 0000000233333720
authors.initials: PS
authors.lastname: Kannan
authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, Australia.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Kemp
authors.affiliation: Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, Australia.
authors.forename: John P
authors.initials: JP
authors.lastname: Newnham
authors.affiliation: Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Jobe
authors.affiliation: Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Suhas G
authors.initials: SG
authors.lastname: Kallapur
mesh_terms: D000653:Amniotic Fluid / Q000378:metabolism*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D002821:Chorioamnionitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D005865:Gestational Age; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000254:growth & development / Q000378:metabolism*; D011247:Pregnancy; D047928:Premature Birth; D012333:RNA, Messenger / Q000378:metabolism; D012756:Sheep; D013997:Time Factors
chemical_list: D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D012333:RNA, Messenger
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