Helicobacter hepaticus induces an inflammatory response in primary human hepatocytes

• Published in: PloS one 2014-06, Vol.9 (6), p.e99713
• Main Authors: Kleine, Moritz, Worbs, Tim, Schrem, Harald, Vondran, Florian W R, Kaltenborn, Alexander, Klempnauer, Jürgen, Förster, Reinhold, Josenhans, Christine, Suerbaum, Sebastian, Bektas, Hüseyin
• Format: Article
• Language: English
• Subjects: Analgesics; Aspartate Aminotransferases - metabolism; Bacteria; Bile; Cell activation; Cell adhesion; Cell culture; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell membranes; Cells, Cultured; Coculture Techniques; Conditioning; Cultivation; Culture media; Culture Media, Conditioned - pharmacology; Cyclooxygenase 2 - biosynthesis; Cyclooxygenase-2; Cytochrome; Cytochrome P450; Cytokines; Cytokines - metabolism; Dinoprostone - biosynthesis; Enzyme Induction - drug effects; Enzyme-linked immunosorbent assay; Epidemiology; Gastroenterology; Gene expression; Gene Expression Regulation - drug effects; Helicobacter hepaticus - drug effects; Helicobacter hepaticus - physiology; Hepatitis; Hepatocellular carcinoma; Hepatocytes; Hepatocytes - drug effects; Hepatocytes - enzymology; Hepatocytes - microbiology; Hepatocytes - pathology; Hepatology; Human behavior; Humans; Immunology; Infections; Inflammation; Inflammation - pathology; Inflammatory response; Intercellular adhesion molecule 1; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Interleukin 1; Interleukin 8; Liver; Liver cancer; Medical schools; Medicine and Health Sciences; Membranes; Microscopy; Microscopy, Fluorescence, Multiphoton; Models, Biological; Monocyte chemoattractant protein 1; Monocytes; Monocytes - drug effects; Monocytes - metabolism; Morphology; Motility; Neutrophils; Prostaglandin E2; Proteins; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Surgery; Synthesis; Tumor necrosis factor-α
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0099713

Helicobacter hepaticus can lead to chronic hepatitis and hepatocellular carcinoma in certain strains of mice. Until now the pathogenic role of Helicobacter species on human liver tissue is still not clarified though Helicobacter species identification in human liver cancer was successful in case controlled studies. Therefore we established an in vitro model to investigate the interaction of primary human hepatocytes (PHH) with Helicobacter hepaticus. Successful co-culturing of PHH with Helicobacter hepaticus was confirmed by visualization of motile bacteria by two-photon-microscopy. Isolated human monocytes were stimulated with PHH conditioned media. Changes in mRNA expression of acute phase cytokines and proteins in PHH and stimulated monocytes were determined by Real-time PCR. Furthermore, cytokines and proteins were analyzed in PHH culture supernatants by ELISA. Co-cultivation with Helicobacter hepaticus induced mRNA expression of Interleukin-1 beta (IL-1β), Tumor necrosis factor-alpha, Interleukin-8 (IL-8) and Monocyte chemotactic protein-1 (MCP-1) in PHH (p