Intra-amniotic infections (IAI) are one of the reasons for preterm birth. High mobility group box 1 (HMGB1) is a nuclear protein with various physiological functions, including tissue healing. Its excessive extracellular release potentiates inflammatory reaction and can revert its action from beneficial to detrimental. We infected the amniotic fluid of a pig on the 80th day of gestation with 1 × 104 colony forming units (CFUs) of E. coli O55 for 10 h, and evaluated the appearance of HMGB1, receptor for glycation endproducts (RAGE), and Toll-like receptor (TLR) 4 in the amniotic membrane and fluid. Sham-infected amniotic fluid served as a control. The expression and release of HMGB1 were evaluated by Real-Time PCR, immunofluorescence, immunohistochemistry, and ELISA. The infection downregulated HMGB1 mRNA expression in the amniotic membrane, changed the distribution of HMGB1 protein in the amniotic membrane, and increased its level in amniotic fluid. All RAGE mRNA, protein expression in the amniotic membrane, and soluble RAGE level in the amniotic fluid were downregulated. TLR4 mRNA and protein expression and soluble TLR4 were all upregulated. HMGB1 is a potential target for therapy to suppress the exaggerated inflammatory response. This controlled expression and release can, in some cases, prevent the preterm birth of vulnerable infants. Studies on suitable animal models can contribute to the development of appropriate therapy.
- MeSH
- amnion imunologie mikrobiologie patologie MeSH
- Escherichia coli růst a vývoj patogenita MeSH
- infekce vyvolané Escherichia coli genetika imunologie mikrobiologie veterinární MeSH
- infekční komplikace v těhotenství genetika imunologie mikrobiologie veterinární MeSH
- interakce hostitele a patogenu genetika imunologie MeSH
- lidé MeSH
- messenger RNA genetika imunologie MeSH
- modely nemocí na zvířatech MeSH
- plodová voda imunologie mikrobiologie MeSH
- prasata MeSH
- předčasný porod prevence a kontrola MeSH
- protein HMGB1 genetika imunologie MeSH
- receptor pro konečné produkty pokročilé glykace genetika imunologie MeSH
- regulace genové exprese MeSH
- signální transdukce MeSH
- těhotenství MeSH
- toll-like receptor 4 genetika imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Spontaneous preterm birth significantly contributes to the overall neonatal morbidity associated with preterm deliveries. Nearly 50% of cases are associated with microbial invasion of the amniotic cavity followed by an inflammatory response. Robust diagnostic tools for neonates jeopardized by infection and inflammation may thus decrease the overall neonatal morbidity substantially. Amniotic fluid retrieved during labor retains fetal and pregnancy-related protein fingerprint and its sampling does not place any unwanted stress on women. Using exploratory and targeted methods we analyzed proteomes of amniotic fluid sampled at the end of spontaneous preterm labor prior to delivery from women with and without infection and inflammation. Exploratory data indicated several amniotic fluid proteins to be associated with infectious-inflammatory complications in spontaneous preterm birth. LC-SRM analysis subsequently verified statistically significant changes in lipocalin-1 (P = 0.047 and AUC = 0.67, P = 0.046), glycodelin (P = 0.013 and AUC = 0.73, P = 0.013), and nicotinamide phosphoribosyltransferase (P = 0.018 and AUC = 0.71, P = 0.01).
- MeSH
- dospělí MeSH
- infekční komplikace v těhotenství genetika patologie MeSH
- lidé MeSH
- peptidové mapování MeSH
- peripartální období genetika MeSH
- plodová voda metabolismus MeSH
- předčasný porod genetika patologie MeSH
- proteom genetika MeSH
- těhotenství MeSH
- zánět komplikace genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- chronická nemoc klasifikace ošetřování MeSH
- dospělí psychologie MeSH
- infekční komplikace v těhotenství genetika klasifikace MeSH
- lidé anatomie a histologie fyziologie MeSH
- pyelonefritida MeSH
- retrospektivní studie MeSH
- těhotenství genetika MeSH
- Check Tag
- dospělí psychologie MeSH
- lidé anatomie a histologie fyziologie MeSH
- mužské pohlaví MeSH
- těhotenství genetika MeSH
- ženské pohlaví MeSH