Syk tyrosine kinase participates in beta1-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 nonhematopoietic 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. With the use of 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 in primary cells and the cell lines HS-24 and BEAS-2B. Syk-dependent signaling pathways in EC were initiated by engagement of beta1-integrin receptors. Stimulation of beta1-integrin receptors by fibronectin or antibody cross-linking caused redistribution of Syk from a cytoplasmic to plasma membrane localization. In stimulated cells, Syk and beta1-integrin colocalized. In addition, following beta1-integrin receptor engagement, tyrosine phosphorylation of Syk was observed. Expression of the intercellular adhesion molecule-1 (ICAM-1) and production of IL-6, both important molecules in lung inflammation, was downregulated 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.
Ulanova
Marina
M
Department of medicine, University of Alberta, Edmonton, Alberta, Canada. mulanova@ualberta.ca
Puttagunta
Lakshmi
L
Marcet-Palacios
Marcelo
M
Duszyk
Marek
M
Steinhoff
Ulrich
U
Duta
Florentina
F
Kim
Moo-Kyung
MK
Indik
Zena K
ZK
Schreiber
Alan D
AD
Befus
A Dean
AD
D000818:Animals; D001980:Bronchi / Q000378:metabolism*; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000494:pharmacology; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D039081:Integrin alpha5beta1 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011914:Rats, Inbred BN; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology; D014018:Tissue Distribution / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051746:ZAP-70 Protein-Tyrosine Kinase
D003432:Cross-Linking Reagents; D018836:Inflammation Mediators; D039081:Integrin alpha5beta1; D019012:Integrin beta1; D015850:Interleukin-6; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C041525:3,3',4,5'-tetrahydroxystilbene; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; C497262:Zap70 protein, mouse