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2009/03/17 |
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16:00/16:50 |
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馬志遠 |
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凌 斌 |
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無 |
http://basicmed.med.ncku.edu.tw/admin/up_img/980317-2.pdf TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-β Jonathan C Kagan, Tian Su, Tiffany Horng, Amy Chow, Shizuo Akira & Ruslan Medzhitov Nat Immunol 9, 361-368 (2008). Speaker: Chih-Yuan Ma Date: 2009.3.17 (16:00-16:50) Commentator: Pin Ling, Ph.D. Room: 602 Abstract Pattern-recognition receptors (PRRs) play important roles in innate immunity. They can recognize pathogen-associated molecular patterns (PAMPs) and in turn activate immune defense. Toll-like receptors (TLRs) belong to the family of PRRs and regulate innate immunity against microbial infection in humans. Toll-like receptor 4 (TLR4) is the well-characterized TLR and induces two distinct signaling pathways when stimulated with lipopolysaccharide (LPS). One is the TIRAP-MyD88 pathway which stimulates the production of proinflammatory cytokines, and the other is TRAM-TRIF pathway which elicit the expression of type I interferon. However, the reason why TLR4 uses these two different pathways in response to LPS is still unclear. In this study, the authors found that inhibition of endocytosis by a specific inhibitor of dynamin called dynasore could disrupt TRAM-TRIF-dependent signaling but not TIRAP-MyD88-dependent signaling. They also demonstrated that TRAM contains a bipartite localization motif that controls the subcellular distribution of TRAM and regulates TRAM-TRIF pathway. Taken together, they propose that TLR4 induces TRAM-TRIF signaling pathway from endosomal compartment and then triggers the expression of type I interferon. Furthermore, they found that TRAF3 is a critical factor in the production of interferon and the localization of TRAF3 regulates interferon-producing ability. This study provides a new model of TLR References 1. Akira, S., Uematsu, S. & Takeuchi, O. Pathogen recognition and innate immunity. Cell 124, 783-801 (2006). 2. Oganesyan, G. et al. Critical role of TRAF
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