Spleen tyrosine kinase (Syk) as a novel target for allergic asthma and rhinitis.
Allergic asthma and rhinitis are prevalent diseases in the modern world, both marked by inflammation of the airways. The spleen tyrosine kinase (Syk) plays a critical role in the regulation of such immune and inflammatory responses. Although Syk is best known as a key component of immunoreceptor signalling complexes in leukocytes, recent studies demonstrated Syk expression in cells outside the haematopoietic lineage. Moreover, in recent years, it has been established that Syk is involved in various signalling cascades including those originating from integrin and cytokine receptors. Thus, Syk likely has a much wider biological role than previously recognised. Specific inhibition of Syk using aerosolised antisense oligonucleotides in liposome complexes significantly decreased lung inflammatory responses in experimental asthma and acute lung injury models. In addition, pharmacological inhibitors of Syk have been recently developed with potential for use as therapeutics. However, in the development and the rational delivery of drugs targeting Syk, it is important to consider the multiple cell types that express this kinase and the potential effects of its inhibition on various physiological functions. This review focuses on the recent data and the emerging ideas about Syk as a therapeutic target.
Ulanova
Marina
M
University of Alberta, Department of Medicine, Edmonton, Alberta, T6G 2S2, Canada.
Duta
Florentina
F
Puttagunta
Lakshmi
L
Schreiber
Alan D
AD
Befus
A Dean
AD
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012220:Rhinitis / Q000188:drug therapy* / Q000201:enzymology; D000072377:Syk Kinase
D018926:Anti-Allergic Agents; D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase