Altered gene expression in acute systemic inflammation detected by complete coverage of the human liver transcriptome

Authors

  • Cédric Coulouarn,

    1. INSERM Unité 519 and Faculté de Médecine-Pharmacie, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides, Rouen, France
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  • Grégory Lefebvre,

    1. INSERM Unité 519 and Faculté de Médecine-Pharmacie, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides, Rouen, France
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  • Céline Derambure,

    1. INSERM Unité 519 and Faculté de Médecine-Pharmacie, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides, Rouen, France
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  • Thierry Lequerre,

    1. INSERM Unité 519 and Faculté de Médecine-Pharmacie, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides, Rouen, France
    2. Service de Rhumatologie, Rouen, France
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  • Michel Scotte,

    1. INSERM Unité 519 and Faculté de Médecine-Pharmacie, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides, Rouen, France
    2. Service de Chirurgie Générale et Digestive, Rouen, France
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  • Arnaud Francois,

    1. Département de Pathologie, Centre Hospitalier Universitaire, Rouen, France
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  • Dominique Cellier,

    1. Laboratoire de Mathématiques Raphaël Salem and UMR CNRS 6085, Université de Rouen, Rouen, France
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  • Maryvonne Daveau,

    1. INSERM Unité 519 and Faculté de Médecine-Pharmacie, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides, Rouen, France
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  • Jean-Philippe Salier

    Corresponding author
    1. INSERM Unité 519 and Faculté de Médecine-Pharmacie, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides, Rouen, France
    • INSERM Unité 519, Faculté de Médecine-Pharmacie, 22 Bvd. Gambetta, 76183 Rouen cedex, France
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    • fax: +33-235-14-85-41


Abstract

The goal of the current study was to provide complete coverage of the liver transcriptome with human probes corresponding to every gene expressed in embryonic, adult, and/or cancerous liver. We developed dedicated tools, namely, the Liverpool nylon array of complementary DNA (cDNA) probes for approximately 10,000 nonredundant genes and the LiverTools database. Inflammation-induced transcriptome changes were studied in liver tissue samples from patients with an acute systemic inflammation and from control subjects. One hundred and fifty-four messenger RNAs (mRNA) correlated statistically with the extent of inflammation. Of these, 134 mRNA samples were not associated previously with an acute-phase (AP) response. The hepatocyte origin and proinflammatory cytokine responsiveness of these mRNAs were confirmed by quantitative reverse-transcription polymerase chain reaction (Q-RT-PCR) in cytokine-challenged hepatoma cells. The corresponding gene promoters were enriched in potential binding sites for inflammation-driven transcription factors in the liver. Some of the corresponding proteins may provide novel blood markers of clinical relevance. The mRNAs whose level is most correlated with the AP extent (P < .05) were enriched in intracellular signaling molecules, transcription factors, glycosylation enzymes, and up-regulated plasma proteins. In conclusion, the hepatocyte responded to the AP extent by fine tuning some mRNA levels, controlling most, if not all, intracellular events from early signaling to the final secretion of proteins involved in innate immunity. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2004;39:353–364.)

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