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Molecular mechanisms involved in TNF - and gastrin-mediated gene regulation

Thommesen, Liv
Doctoral thesis
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http://hdl.handle.net/11250/263087
Date
2001
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  • Fakultet for medisin og helsevitenskap (uspesifisert) [227]
Abstract
Cells in a multicellular organism depend on extensive communication with each other. Eukaryotic cells have developed elaborate signal transduction systems by which externally provided information (hormones, cytokines, growth factors, ions and other signaling molecules) is converted into intracellular information that regulates the internal workings of the cell, such as transcription of genes. This can be exemplified by gastric acid production in humans. Secretion of gastric acid is regulated by the peptide hormone gastrin, and involves an interplay between different cells in the stomach mucosa as well as induction of gene expression (Figure 1). The physiological response to food intake includes release of gastrin from G-cells. Gastrin binds to receptors on the ECL-cells and thereby induces histamine release from internal vesicles. Histamine in turn acts upon parietal cells that are stimulated to produce and secrete gastric acid. The regulatory functions of gastrin also include release of somatostatin from D-cells and induction of histidine decarboxylase (HDC) gene expression. HDC catalyses the ratelimiting step in histamine production in ECL-cells.
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Lægreid, A; Thommesen, L; Jahr, TG; Sundan, A; Espevik, T. Tumor Necrosis Factor Induces Lipopolysaccharide Tolerance in a Human Adenocarcinoma Cell Line Mainly through the TNF p55 Receptor (*). Journal of Biological Chemistry. 270(43): 25418-25425, 1995.

Thommesen, L; Sjursen, W; Gåsvik, K; Hanssen, W; Brekke, O-L; Skattebøl, L; Holmeide, AK; Espevik, T; Johansen, B; Lægreid, A. Selective Inhibitors of Cytosolic or Secretory Phospholipase A2 Block TNF-Induced Activation of Transcription Factor Nuclear Factor-B and Expression of ICAM-1. J. Immunol. 161: 3421-3430, 1998.

Thommesen, L; Nørsett, K; Sandvik, AK; Hofsli, E; Lægreid, A. Regulation of Inducible cAMP Early Repressor Expression by Gastrin and Cholecystokinin in the Pancreatic Cell Line AR42J. J. Biol. Chem. 275: 4244-4250, 2000.
Publisher
Det medisinske fakultet
Series
Dissertations at the Faculty of Medicine, 0805-7680; 189

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