Regulation and possible function of beta-catenin in human monocytes

• Published in: The Journal of immunology (1950) 2001-12, Vol.167 (12), p.6786-6793
• Main Authors: Thiele, A, Wasner, M, Müller, C, Engeland, K, Hauschildt, S
• Format: Article
• Language: English
• Subjects: Androstadienes - pharmacology; b-catenin; beta Catenin; Cadherins - metabolism; Cell Adhesion; Cells, Cultured; Culture Media - pharmacology; Cytoskeletal Proteins - metabolism; Cytoskeletal Proteins - physiology; DNA-Binding Proteins - physiology; Enzyme Inhibitors - pharmacology; Humans; Kinetics; LEF protein; Lipopolysaccharides - pharmacology; Lymphoid Enhancer-Binding Factor 1; Monocytes - drug effects; Monocytes - immunology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; RNA, Messenger - biosynthesis; TCF protein; TCF Transcription Factors; Trans-Activators; Transcription Factor 7-Like 2 Protein; Transcription Factors - genetics; Transcription Factors - physiology; Transcriptional Activation; Tumor Cells, Cultured; Wortmannin; Zymosan - pharmacology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.12.6786

In this study, we demonstrate that adherence factors, serum constituents, LPS, and zymosan are capable of inducing a cellular accumulation of beta-catenin in human monocytes. Whereas adherence-dependent accumulation of beta-catenin can be blocked by wortmannin, an inhibitor of phosphatidylinositol 3-kinase, accumulation induced by the remaining stimuli cannot be prevented by inhibition of phosphatidylinositol 3-kinase, implying the involvement of beta-catenin in other not yet described signal transduction pathways. A role of beta-catenin in adherence-dependent processes by interacting with classical cadherins can be excluded as we could not detect cadherins in monocytes. To test whether it is possible that beta-catenin interacts with LEF/TCF (lymphoid enhancer factor/T cell factor) transcription factors, we studied the expression of this protein family. TCF-4 was identified as the LEF/TCF transcription factor present in human monocytes. However, neither cellular induction of beta-catenin nor cotransfection experiments with beta-catenin conducted in the monocytic cell line THP-1 resulted in the activation of a LEF/TCF-dependent promoter, suggesting the requirement of additional signals. Concurrent with this suggestion, we found that LPS and zymosan, two physiological inducers of beta-catenin, caused an increase in the expression of genes that are positively regulated by beta-catenin.