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

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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)-1, 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.

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.

Results:IL-1, IL-1β, IL-6, IL-8, IL-10, MCP-1, and tumor necrosis factor (TNF)- 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.

Original languageEnglish (US)
Pages (from-to)441-447
Number of pages7
JournalPediatric Research
Volume76
Issue number5
DOIs
StatePublished - Nov 5 2014
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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