TY - JOUR
T1 - Intra-amniotic LPS modulates expression of antimicrobial peptides in the fetal sheep lung
AU - Schmidt, Augusto F.
AU - Kannan, Paranthaman S.
AU - Kemp, Matthew W.
AU - Kramer, Boris W.
AU - Newnham, John P.
AU - Jobe, Alan H.
AU - Kallapur, Suhas G.
PY - 2014/11
Y1 - 2014/11
N2 - 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.
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)-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.
U2 - 10.1038/pr.2014.113
DO - 10.1038/pr.2014.113
M3 - Article
C2 - 25105257
SN - 0031-3998
VL - 76
SP - 441
EP - 447
JO - Pediatric Research
JF - Pediatric Research
IS - 5
ER -