Outside-in signaling in airway epithelial cells

Airway epithelial cells (EC) participate in lung inflammatory responses. They can be activated through several cell surface receptors, such as integrins that mediate cell-cell and cell-extracellular matrix interactions. Signal transduction in EC is poorly understood. We hypothesized that the protein...

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Published in:Journal of allergy and clinical immunology 2004-02, Vol.113 (2), p.S324-S324
Main Authors: Ulanova, M., Puttagunta, L., Schreiber, A.D., Befus, A.D.
Format: Article
Language:English
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Summary:Airway epithelial cells (EC) participate in lung inflammatory responses. They can be activated through several cell surface receptors, such as integrins that mediate cell-cell and cell-extracellular matrix interactions. Signal transduction in EC is poorly understood. We hypothesized that the protein tyrosine kinase Syk participates in integrin β1 mediated activation of lung EC. To detect protein expression, immunohistochemistry, immunoprecipitation, Western blot, confocal microscopy, and flow cytometry were used. Syk expression was detected in human and rodent bronchial epithelium in situ and in bronchial epithelial cell lines HS-24 and BEAS-2B. To investigate participation of Syk in integrin-mediated signaling, EC were stimulated by fibronectin, a natural integrin β1 ligand, or by antibody cross-linking. Stimulation under both adherent and non-adherent conditions induced translocation of Syk from a nuclear and perinuclear area to a diffuse cytoplasmic and plasma membrane localization. Stimulation induced co-localization of Syk and integrin β1 at focal adhesions. Integrin β1 co-precipitated with Syk in stimulated EC demonstrating interaction between these two molecules. In addition, Syk phosphorylation on tyrosine occurred as a result of cell activation, along with phosphorylation of FAK. Syk kinase is involved in outside-in signaling initiated by engagement of integrin β1 in airway EC. Syk-dependent signaling pathways may regulate EC function(s). Knowledge of Syk-dependent signaling should help to understand the role of airway EC in inflammation and may provide a new therapeutic target.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2004.01.669