Ruili Sun

Wuhan University, Wu-han-shih, Hubei, China

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Publications (4)12.59 Total impact

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    ABSTRACT: Toll-like receptor 3 (TLR3), a member of the pathogen recognition receptors, is widely expressed in various cells and has been shown to activate immune signaling pathways by recognizing viral double-stranded RNA (dsRNA). Recently, it was reported that the activation of TLR3 induced apoptosis in some cells, but the detailed molecular mechanism is not fully understood. In this study, we found that in endothelial cells, polyinosinic-polycytidylic acid (poly I:C) induced dose- and time-dependent cell apoptosis, which was elicited by TLR3 activation, as TLR3 neutralization and down-regulation repressed the apoptosis. Poly I:C induced the activation of both the caspases 8 and 9, indicating that TLR3 triggered the signaling of both the extrinsic and intrinsic apoptotic pathways. Poly I:C up-regulated tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors, death receptors 4/5 (DR4/5), resulting in the initiating of the extrinsic pathway. Futhermore, poly I:C down-regulated anti-apoptotic protein, B cell lymphoma 2 (Bcl-2), and up-regulated Noxa, a key Bcl-2 homology 3 (BH3)-only antagonist of Bcl-2, leading to the priming of the intrinsic pathway. A p53-related protein, the transactivating p63 isoform α (TAp63α) was induced by TLR3 activation and contributed to the activation of both the intrinsic and extrinsic apoptotic pathways. Both the cells deficient in p63 gene expression by RNA interference, and cells over-expressed the amino terminally truncated p63 isoform α (δNp63α), a dominant negative variant of TAp63α, by gene transfection, survived TLR3 activation. Taken together, as a crucial regulator downstream of TLR3, TAp63α induces cell death via death receptors and mitochondria.
    Journal of Biological Chemistry 03/2011; · 4.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Toll-like receptor 3 (TLR3), a member of the pathogen recognition receptors, is widely expressed in various cells and has been shown to activate immune signaling pathways by recognizing viral double-stranded RNA. Recently, it was reported that the activation of TLR3 induced apoptosis in some cells, but the detailed molecular mechanism is not fully understood. In this study, we found that in endothelial cells polyinosinic-polycytidylic acid (poly(I-C)) induced dose- and time-dependent cell apoptosis, which was elicited by TLR3 activation, as TLR3 neutralization and down-regulation repressed the apoptosis. Poly(I-C) induced the activation of both caspases 8 and 9, indicating that TLR3 triggered the signaling of both the extrinsic and intrinsic apoptotic pathways. Poly(I-C) up-regulated tumor necrosis factor-related apoptosis-inducing ligand and its receptors, death receptors 4/5, resulting in initiating the extrinsic pathway. Furthermore, poly(I-C) down-regulated anti-apoptotic protein, B cell lymphoma 2 (Bcl-2), and up-regulated Noxa, a key Bcl-2 homology 3-only antagonist of Bcl-2, leading to the priming of the intrinsic pathway. A p53-related protein, the transactivating p63 isoform α (TAp63α), was induced by TLR3 activation and contributed to the activation of both the intrinsic and extrinsic apoptotic pathways. Both the cells deficient in p63 gene expression by RNA interference and cells that overexpressed the N-terminally truncated p63 isoform α (ΔNp63α), a dominant-negative variant of TAp63α, by gene transfection, survived TLR3 activation. Taken together, TAp63α is a crucial regulator downstream of TLR3 to induce cell death via death receptors and mitochondria.
    Journal of Biological Chemistry 03/2011; 286(18):15918-28. · 4.65 Impact Factor
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    ABSTRACT: Toll-like receptor 3 (TLR3), a receptor for viral double strain RNA (dsRNA), mediates anti-viral immune response by activating the innate immunity and cross-priming CD8(+) T cells. TLR3 agonists can directly trigger apoptosis in human cancer cells, and have been used as adjuvants to treat cancer patients with the aim of inducing an IFN-dependent immune response. In this study, we examined the effect of TLR3 activation on the metastasis of nasopharyngeal carcinoma (NPC). We found that NPC cells expressed TLR3 gene transcript and protein. TLR3 activation downregulated the expression of chemokine receptor CXCR4 in a dose-dependent manner, and inhibited cell migration in response to CXCR4 ligand stromal cell-derived factor-1alpha (SDF-1alpha) in chemotaxis assays. Furthermore, TLR3 activation significantly reduced the capacity of NPC cells to form metastasis in draining lymph nodes when injected in athymic mice. The anti-metastasis activity of endogenous human TLR3 expression in cancer cells reveals a novel aspect of the multiple-faced TLR biology, which may open new clinical prospects for using TLR3 agonists to control cancer metastasis in selected cancers.
    Cancer biology & therapy 11/2009; 8(19):1826-30. · 3.29 Impact Factor
  • Cancer Biology & Therapy - CANCER BIOL THER. 01/2009; 8(19):1826-1830.

Publication Stats

40 Citations
12.59 Total Impact Points

Institutions

  • 2011
    • Wuhan University
      Wu-han-shih, Hubei, China
    • Renmin University of China
      Peping, Beijing, China
  • 2009
    • Central South University
      • Cancer Research Institute
      Changsha, Hunan, China