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.

• Keywords
• Toll-like receptor, amniotic fluid, amniotic membrane, cytokines, high mobility group box 1, intra-amniotic infection, pig, preterm birth, receptor for advanced glycation endproducts,
• MeSH
• Amnion immunology   microbiology   pathology   MeSH
• Escherichia coli growth & development   pathogenicity   MeSH
• Escherichia coli Infections genetics   immunology   microbiology   veterinary   MeSH
• Pregnancy Complications, Infectious genetics   immunology   microbiology   veterinary   MeSH
• Host-Pathogen Interactions genetics   immunology   MeSH
• Humans MeSH
• RNA, Messenger genetics   immunology   MeSH
• Disease Models, Animal MeSH
• Amniotic Fluid immunology   microbiology   MeSH
• Swine MeSH
• Premature Birth prevention & control   MeSH
• HMGB1 Protein genetics   immunology   MeSH
• Receptor for Advanced Glycation End Products genetics   immunology   MeSH
• Gene Expression Regulation MeSH
• Signal Transduction MeSH
• Pregnancy MeSH
• Toll-Like Receptor 4 genetics   immunology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• RNA, Messenger MeSH
• HMGB1 Protein MeSH
• Receptor for Advanced Glycation End Products MeSH
• Toll-Like Receptor 4 MeSH

The pig amnion was in vivo intraamniotically infected with E. coli for 10 h at 80-85 d of gestation either with the nonpathogenic O86 strain or enteropathogenic O55 strain. TNF-alpha, IL-10, IL-1beta and IFN-gamma were determined in amniotic fluids by ELISA, the expression of cytokines and some other inflammatory markers was determined by immunohistochemistry. Intraamniotic infection induced high levels of TNF-alpha in amniotic fluids which correlated with bacterial virulence whereas IL-10 was induced only by O86. The IL-1beta level did not increase significantly and was expressed in all infected membranes. IFN-gamma was negligible or absent. TNF-alpha, IL-12p40, calprotectin, HSP65 and gp91phox were found by immunohistochemistry only in amnion membranes infected with the enteropathogenic strain 055.

• MeSH
• Amnion immunology   microbiology   MeSH
• Biomarkers metabolism   MeSH
• Cytokines metabolism   MeSH
• Escherichia coli immunology   pathogenicity   MeSH
• Escherichia coli Infections immunology   microbiology   veterinary   MeSH
• Pregnancy Complications, Infectious immunology   microbiology   veterinary   MeSH
• Interferon-gamma metabolism   MeSH
• Interleukin-1 metabolism   MeSH
• Interleukin-10 metabolism   MeSH
• Swine Diseases immunology   microbiology   MeSH
• Swine MeSH
• Pregnancy MeSH
• Tumor Necrosis Factor-alpha metabolism   MeSH
• Inflammation immunology   MeSH
• Animals MeSH
• Check Tag
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biomarkers MeSH
• Cytokines MeSH
• Interferon-gamma MeSH
• Interleukin-1 MeSH
• Interleukin-10 MeSH
• Tumor Necrosis Factor-alpha MeSH

The increasing development of bacterial resistance to traditional antibiotics has reached alarming levels, thus creating a strong need to develop new antimicrobial agents. These new antibiotics should possess novel mechanisms of action and different cellular targets compared with existing antimicrobials. Recent discoveries and isolations of so-called animal antibiotics, mostly small cationic peptides, which represent a potent branch of natural immunity, offered the possibility to acquire new and effective antibiotics of this provenance. To this date, more than 500 antibiotic peptides have been distinguished and defined. Their antimicrobial properties present new opportunities for their use as antibiotics or for construction of their more effective derivatives, but much research is still required to pave the way to their practical use. This is a survey of substances forming an armamentarium of natural immunity of mammals.

• MeSH
• Anti-Bacterial Agents metabolism   pharmacology   MeSH
• Bacteria drug effects   MeSH
• Bacterial Infections immunology   MeSH
• Eosinophils immunology   metabolism   MeSH
• Humans MeSH
• Macrophages immunology   metabolism   MeSH
• Neutrophils immunology   metabolism   MeSH
• Peptides * MeSH
• Immunity, Innate * MeSH
• Blood Platelets immunology   metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Peptides * MeSH