Syk Tyrosine Kinase Participates in 1 Integrin Signaling and Inflammatory Responses in Airway Epithelial Cells

The protein tyrosine kinase Syk is critically involved in immunoreceptor signaling in hematopoietic cells. Recent studies demonstrate Syk expression in non-hematopoietic cells, including fibroblasts, endothelial cells, hepatocytes, and breast epithelium. However, the role of Syk in these cells is uncertain. We hypothesized that Syk is expressed in respiratory epithelial cells (EC) and that it functions as a signaling molecule involved in inflammatory responses in the epithelium. Using immunohistochemistry, Western blot, PCR, and laser scanning confocal microscopy, Syk was detected in human, rat and mouse bronchial epithelium in situ and in cultured human bronchial EC, both primary cells and the cell lines HS-24 and BEAS-2B. Syk-dependent signaling pathways in EC were initiated by engagement of 1 integrin receptors. Stimulation of 1 integrin receptors by fibronectin or antibody cross-linking caused redistribution of Syk from a cytoplasmic to plasma membrane localization. In stimulated cells, Syk and integrin 1 co-localized. In addition, following 1 integrin receptor engagement, tyrosine phosphorylation of Syk was observed. Expression of the adhesion molecule ICAM-1 and production of IL-6, both important molecules in lung inflammation, was down-regulated in EC treated with Syk small interfering RNA or Syk inhibitor piceatannol. We propose that Syk is involved in signaling pathways induced by integrin engagement in airway EC. Syk-mediated signaling regulates IL-6 and ICAM-1 expression and may be important in the pathophysiology of lung inflammation.