Elucidation of the role of Bruton's tyrosine kinase in toll-like receptor 3 signaling.

Elucidation of the role of Bruton’s Tyrosine Kinase In Toll-Like Receptor 3 Signaling by Yue Shin Yen Abstract Toll-like receptors (TLR) are responsible for activating host defense defense against various pathogen and microorganisms. Recognition of pathogen-associated molecular patterns (PAM...

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Bibliographic Details
Main Author: Yue, Shin Yen.
Other Authors: Lam, Kong Peng
Format: Final Year Project
Language:English
Published: 2008
Subjects:
Online Access:http://hdl.handle.net/10356/13572
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Institution: Nanyang Technological University
Language: English
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Summary:Elucidation of the role of Bruton’s Tyrosine Kinase In Toll-Like Receptor 3 Signaling by Yue Shin Yen Abstract Toll-like receptors (TLR) are responsible for activating host defense defense against various pathogen and microorganisms. Recognition of pathogen-associated molecular patterns (PAMPs) by various TLRs activates innate immune system. Poly:IC, a synthetic oilgonucloetide which mimic double-stranded RNA binds to TLR3 and activates TRIF-dependent signal transduction cascade. I showed here that Bruton’s tyrosine kinase (Btk) is involved in TLR3 signaling in macrophages and B lymphocytes. Phosphorylated Btk upon poly:IC stimulation in bone marrow-derived macrophages (BMDM). Btk-deficient BMDM secreted less IL-10, IL-12, IL-6 and IFNβ cytokines compare to wildtype BMDM upon poly:IC stimulation. The defective cytokine production may be due to an impaired ERK and IRF3 activation. Absence of Btk also resulted in reduced expression of RANTES/ CCL5, chemokine mRNA. In addition, studies with CBA/Ca and xid B lymphocytes treated with poly:IC demonstrated that IL-10 cytokine production was reduced and suggested that Pleckstrin Homology (PH) domain of Btk is important for Btk activities. Taken together, these finding indicated that Btk plays a key role in TLR3 signaling by positively regulating major downstream signaling transduction events leading to an effective anti-viral response.