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TRAIL

Novel TRAIL Isoform and Multimerized TRAIL Mimics for Specific Cell Apoptosis Studies

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A proposed model for TRAIL regulating inflammation resolution by modulation of neutrophil lifespan. In WT mice, TRAIL expression by tissue cells, e.g., the respiratory epithelium, can induce apoptosis of recruited neutrophils. In TRAIL-deficient mice, inflammatory cell survival is prolonged until engagement of a constitutive program of neutrophil apoptosis. Exogenous TRAIL accelerates the apoptotic death of neutrophils in TRAIL-deficient and WT mice.

Figure from : McGrath E.E. et al., J Leukoc Biol. Nov 2011; 90(5): 855–865. doi: 10.1189/jlb.0211062

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Isolation of a TRAIL antagonist from the serum of HIV-infected patients.

Virus-host interactions are characterized by the selection of adaptive mechanisms by which to evade pathogenic and defense mechanisms, respectively. In primary T cells infected with HIV, HIV infection up-regulates TNF-related apoptosis inducing ligand (TRAIL) and death-inducing TRAIL receptors, but blockade of TRAIL:TRAIL receptor interaction does not alter HIV-induced cell death. Instead, HIV infection results in a novel splice variant that we call TRAIL-short (TRAIL-s), which antagonizes TRAIL-R2. In HIV patients, plasma TRAIL-s concentration increases with increasing viral load and renders cells resistant to TRAIL-induced death. Knockdown of TRAIL-s abrogates this resistance. We propose that TRAIL-s is a novel adaptive mechanism of apoptosis resistance acquired by HIV-infected cells to avoid their elimination by TRAIL-dependent effector mechanism.

Schnepple DJ, Shepard B, Bren GD et al., J Biol Chem. 2011 Oct 14;286(41):35742-54. doi: 10.1074/jbc.M111.274639. Epub 2011 Aug 22.

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Multivalent DR5 peptides activate the TRAIL death pathway and exert tumoricidal activity.

Pavet V, Beyrath J, Pardin C et al., Cancer Res. 2010 Feb 1;70(3):1101-10. doi: 10.1158/0008-5472.CAN-09-2889. Epub 2010 Jan 26.

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TRAIL-beta and TRAIL-gamma: two novel splice variants of the human TNF-related apoptosis-inducing ligand (TRAIL) without apoptotic potential.

Krieg A, Krieg T, Wenzel M et al., Br J Cancer. 2003 Mar 24;88(6):918-27.

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IFNalpha-stimulated neutrophils and monocytes release a soluble form of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2 ligand) displaying apoptotic activity on leukemic cells.

Tecchio C, Huber V, Scapini P et al., Blood. 2004 May 15;103(10):3837-44. Epub 2004 Jan 15.

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Differential activation of TRAIL-R1 and -2 by soluble and membrane TRAIL allows selective surface antigen-directed activation of TRAIL-R2 by a soluble TRAIL derivative.

Wajant H, Moosmayer D, Wüest T et al., Oncogene. 2001 Jul 5;20(30):4101-6.

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