High Mobility Group-Box 1 (HMGB1) levels are increased in amniotic fluid of women with intra-amniotic inflammation-determined preterm birth,and the source may be the damaged fetal membranes |
| |
| Institution: | 1. Coagulation Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel;2. Department of Hematology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel;3. Department of Hematology, Edith Wolfson Medical Center, Holon, Israel;1. Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA;2. Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA;3. Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA |
| |
| Abstract: | BackgroundHigh 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.MethodsWe 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.ResultsAF HMGB1 levels are not gestational age regulated but are increased in women with intra-amniotic inflammation and preterm birth. The likely source is the damaged amniochorion, as demonstrated by immunohistochemistry and explant experiments.ConclusionsOur research supports a role for HMGB1 in the inflammatory response leading to preterm birth. As a delayed phase cytokine, in utero exposure to elevated AF HMGB1 levels may have an impact on the newborn beyond the time of birth. |
| |
| Keywords: | Alarmins DAMPs Endokines Amniochorion Preterm birth Innate immunity |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
