Intra-amniotic LPS modulates expression of antimicrobial peptides in the fetal sheep lung

Augusto F. Schmidt, Paranthaman S. Kannan, Matthew W. Kemp, Boris W. Kramer, John P. Newnham, Alan H. Jobe, Suhas G. Kallapur*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Web of Science)

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 beta-defensin-1 (SBD1), and sheep beta-defensin-2 (SBD2); and DAMPs: interleukin (IL)-1 alpha, 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-1 alpha, IL-1 beta, 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 24h. 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.
Original languageEnglish
Pages (from-to)441-447
JournalPediatric Research
Volume76
Issue number5
DOIs
Publication statusPublished - Nov 2014

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