Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.bbapap.2003.11.013
Title: Tyrosine kinase inhibitors: A new approach for asthma
Authors: Wong, W.S.F. 
Leong, K.P.
Keywords: AHR
Airway hyperresponsiveness
Airway remodeling
Antigen-presenting cell
APC
Asthma
BAL
Bronchoalveolar lavage
Chemokine
Cytokine
Growth factor
Immune receptor
Immunoreceptor tyrosine-based activation motifs
ITAM
NF-κB
Tyrosine kinase inhibitor
Issue Date: 2004
Source: Wong, W.S.F., Leong, K.P. (2004). Tyrosine kinase inhibitors: A new approach for asthma. Biochimica et Biophysica Acta - Proteins and Proteomics 1697 (1-2) : 53-69. ScholarBank@NUS Repository. https://doi.org/10.1016/j.bbapap.2003.11.013
Abstract: The pathogenesis of allergic asthma involves the interplay of inflammatory cells and airway-resident cells, and of their secreted mediators including cytokines, chemokines, growth factors and inflammatory mediators. Receptor tyrosine kinases are important for the pathogenesis of airway remodeling. Activation of epidermal growth factor (EGF) receptor kinase and platelet-derived growth factor (PDGF) receptor kinase leads to hyperplasia of airway smooth muscle cells, epithelial cells and goblet cells. Stimulation of non-receptor tyrosine kinases (e.g. Lyn, Lck, Syk, ZAP-70, Fyn, Btk, Itk) is the earliest detectable signaling response upon antigen-induced immunoreceptor activation in inflammatory cells. Cytokine receptor dimerization upon ligand stimulation induces activation of Janus tyrosine kinases (JAKs), leading to recruitment and phosphorylation of signal transducer and activator of transcription (STAT) for selective gene expression regulation. Activation of chemokine receptors can trigger JAK-STAT pathway, Lck, Fyn, Lyn, Fgr, and Syk/Zap-70 to induce chemotaxis of inflammatory cells. Inhibitors of tyrosine kinases have been shown in vitro to block growth factor-induced hyperplasia of airway-resident cells; antigen-induced inflammatory cell activation and cytokine synthesis; cytokine-mediated pro-inflammatory gene expression in inflammatory and airway cells; and chemokine-induced chemotaxis of inflammatory cells. Recently, anti-inflammatory effects of tyrosine kinase inhibitors (e.g. genistein, tyrphostin AG213, piceatannol, tyrphostin AG490, WHI-P97, WHI-P131, Syk antisense) in animal models of allergic asthma have been reported. Therefore, development of inhibitors of tyrosine kinases can be a very attractive strategy for the treatment of asthma. © 2003 Elsevier B.V. All rights reserved.
Source Title: Biochimica et Biophysica Acta - Proteins and Proteomics
URI: http://scholarbank.nus.edu.sg/handle/10635/32206
ISSN: 15709639
DOI: 10.1016/j.bbapap.2003.11.013
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