PMID- 25105257 OWN - NLM STAT- MEDLINE DCOM- 20151021 LR - 20220408 IS - 1530-0447 (Electronic) IS - 0031-3998 (Print) IS - 0031-3998 (Linking) VI - 76 IP - 5 DP - 2014 Nov TI - Intra-amniotic LPS modulates expression of antimicrobial peptides in the fetal sheep lung. PG - 441-7 LID - 10.1038/pr.2014.113 [doi] AB - 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 beta-defensin-1 (SBD1), and sheep beta-defensin-2 (SBD2); and DAMPs: interleukin (IL)-1alpha, 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-1alpha, IL-1beta, IL-6, IL-8, IL-10, MCP-1, and tumor necrosis factor (TNF)-alpha 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. CONCLUSION: 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. FAU - Schmidt, Augusto F AU - Schmidt AF AD - Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio. FAU - Kannan, Paranthaman S AU - Kannan PS AUID- ORCID: 0000000233333720 AD - Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio. FAU - Kemp, Matthew W AU - Kemp MW AD - School of Women's and Infants' Health, The University of Western Australia, Perth, Australia. FAU - Kramer, Boris W AU - Kramer BW AD - Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands. FAU - Newnham, John P AU - Newnham JP AD - School of Women's and Infants' Health, The University of Western Australia, Perth, Australia. FAU - Jobe, Alan H AU - Jobe AH AD - Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio. FAU - Kallapur, Suhas G AU - Kallapur SG AD - Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio. LA - eng GR - R01 HD057869/HD/NICHD NIH HHS/United States GR - HD-57869/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140808 PL - United States TA - Pediatr Res JT - Pediatric research JID - 0100714 RN - 0 (Antimicrobial Cationic Peptides) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Lipopolysaccharides) RN - 0 (RNA, Messenger) SB - IM MH - Amniotic Fluid/*metabolism MH - Animals MH - Antimicrobial Cationic Peptides/genetics/*metabolism MH - Chorioamnionitis/chemically induced/genetics/*metabolism MH - Cytokines/genetics/metabolism MH - Disease Models, Animal MH - Female MH - Gene Expression Regulation MH - Gestational Age MH - Inflammation Mediators/metabolism MH - *Lipopolysaccharides MH - Lung/growth & development/*metabolism MH - Pregnancy MH - Premature Birth MH - RNA, Messenger/metabolism MH - Sheep MH - Time Factors PMC - PMC4213214 MID - NIHMS598649 EDAT- 2014/08/12 06:00 MHDA- 2015/10/22 06:00 PMCR- 2015/05/01 CRDT- 2014/08/09 06:00 PHST- 2013/11/22 00:00 [received] PHST- 2014/05/11 00:00 [accepted] PHST- 2014/08/09 06:00 [entrez] PHST- 2014/08/12 06:00 [pubmed] PHST- 2015/10/22 06:00 [medline] PHST- 2015/05/01 00:00 [pmc-release] AID - pr2014113 [pii] AID - 10.1038/pr.2014.113 [doi] PST - ppublish SO - Pediatr Res. 2014 Nov;76(5):441-7. doi: 10.1038/pr.2014.113. Epub 2014 Aug 8.