| Summary: | 碩士 === 國立臺灣大學 === 免疫學研究所 === 95 === Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a member of the TNF superfamily which is capable of inducing apoptosis in transformed cells but not in most of the primary cells. In our previous study, we demonstrated that TRAIL stimulated with immobilized DR4, in conjunction with suboptimal anti-CD3, induced T cell proliferation and enhanced IFN-gamma production. This indicates that TRAIL can transduce reverse signal to induce T cell activation. Furthermore, we found that PI3K/Akt activity was enhanced after TRAIL-mediated T cell activation. However, the reverse signaling pathway transduced by TRAIL is still not clear.It has been demonstrated that NF-kappaB was involved in CD28 costimulation signaling pathway, suggesting that NF-kappaB signaling pathway is important in costimulation of T cells. Recent studies have shown that the CARMA1, Bcl10, and MALT1 proteins are critical for the NF-kappaB signaling pathway to the TCR and CD28. Recently studies have confirmed that Akt plays a modulatory role and CARMA1 is required for Akt-mediated in NF-kappaB induction by TCR and CD28. In our previous study, we found that PI3K/Akt activity was enhanced after TRAIL-mediated T cell activation, suggest that PI3K/Akt signaling pathway is involved in TRAIL reverse signaling pathway.
In this study, we use Western blotting to identify the role of NF-kappaB signaling pathway in TRAIL-induced costimulation of T cells. Our results showed that NF-kappaB activation and translocation into nucleus is enhanced in TRAIL-mediated T cell activation. In accordance with this observation is the concomitant enhanced degradation of IkappaB-alpha. Furthermore, TRAIL-mediated T cell proliferation and IL-2 production was significantly decreased by NF-kappaB inhibitor, indicating that NF-kappaB signaling pathway is involved in TRAIL-induced activation of T cells. Moreover, we directly induced PKC-theta phosphorylation and NF-kappaB translocation with DR4-Fc stimulation alone. These results indicated that TRAIL-reversed signaling in T cells transduce via enhancing NF-kappaB activation.
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