Journal
CYTOKINE
Volume 81, Issue -, Pages 82-87Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2016.02.013
Keywords
Alarmins; DAMPs; Endokines; Amniochorion; Preterm birth; Innate immunity
Funding
- National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIH/NICHD) [R01HD062007-01A1]
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Background: High Mobility Group Box-1 (HMGB1) is considered a prototype alarmin molecule. Upon its extracellular release, HMGB1 engages pattern recognition receptors and the Receptor for Advanced Glycation End-products (RAGE) followed by an outpouring of inflammatory cytokines, including interleukin (IL)-6. Methods: We assayed the amniotic fluid (AF) levels of HMGB1 and IL-6 in 255 women that either had a normal pregnancy outcome or delivered preterm. Immunohistochemistry on fetal membranes was used for cellular localization and validation of immunoassay findings. HMGB1 also was analyzed in amniochorion tissue explants subjected to endotoxin. Results: AF HMGB1 levels are not gestational age regulated but are increased in women with intraamniotic inflammation and preterm birth. The likely source is the damaged amniochorion, as demonstrated by immunohistochemistry and explant experiments. Conclusions: Our research supports a role for HMGB1 in the inflammatory response leading to preterm birth. As a delayed phase cytokine, in utero exposure elevated AF HMGB1 levels may have an impact on the newborn beyond the time of birth. (C) 2016 Elsevier Ltd. All rights reserved.
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