Activation of the Canonical β-Catenin Pathway by Histamine

• Published in: The Journal of biological chemistry Vol. 278; no. 52; pp. 52491 - 52496
• Main Authors: Diks, Sander H., Hardwick, James C., Diab, Remco M., van Santen, Marije M., Versteeg, Henri H., van Deventer, Sander J.H., Richel, Dick J., Peppelenbosch, Maikel P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.12.2003
• Subjects: Alkaline Phosphatase - metabolism; b-catenin; beta Catenin; Blotting, Western; Cell Line; Cell Line, Tumor; Cytoskeletal Proteins - metabolism; Dose-Response Relationship, Drug; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; HeLa Cells; histamine; Histamine - metabolism; histamine receptor H1; Humans; In Vitro Techniques; Inflammation; Luciferases - metabolism; Macrophages - metabolism; Phosphorylation; Receptors, Histamine H1 - metabolism; Signal Transduction; Time Factors; Trans-Activators - metabolism; Transcription, Genetic; Transcriptional Activation; Up-Regulation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M310712200

Histamine signaling is a principal regulator in a variety of pathophysiological processes including inflammation, gastric acid secretion, neurotransmission, and tumor growth. We report that histamine stimulation causes transactivation of a T cell factor/β-catenin-responsive construct in HeLa cells and in the SW-480 colon cell line, whereas histamine did not effect transactivation of a construct containing the mutated response construct FOP. On the protein level, histamine treatment increases phosphorylation of glycogen synthase kinase 3-β in HeLa cells, murine macrophages, and DLD-1, HT-29, and SW-480 colon cell lines. Furthermore, histamine also decreases the phosphorylated β-catenin content in HeLa cells and murine macrophages. Finally, pharmacological inhibitors of the histamine H1 receptor counteracted histamine-induced T cell factor/β-catenin-responsive construct transactivation and the dephosphorylation of β-catenin in HeLa cells and in macrophages. We conclude that the canonical β-catenin pathway acts downstream of the histamine receptor H1 in a variety of cell types. The observation that inflammatory molecules, like histamine, activate the β-catenin pathway may provide a molecular explanation for a possible link between inflammation and cancer.