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Double-stranded RNA induces chicken T-cell lymphoma apoptosis by TRIF and NF-κB
Haitao Zou1,2, Ruixue Su1,2, Jing Ruan1,2
1Ministry of Education Key Lab for Avian Preventive Medicine, Yangzhou University, No. 12 East Wenhui Road, Yangzhou, Jiangsu, 225009, P. R. China.
Abstract:
Toll-like receptor-3 (TLR3), a member of the pathogen recognition receptor family, has been reported to activate immune response and to exhibit pro-apoptotic activity against some tumor cells. However it is unclear whether TLR3 has same function against chicken lymphoma. In this paper we investigated the effect of TLR3 activation on a Marek's disease lymphoma-derived chicken cell line, MDCC-MSB1. The TLR3 agonist poly (I:C) activated TLR3 pathway and inhibited tumor cells proliferation through caspase-dependent apoptosis. Using pharmacological approaches, we found that an interferon-independent mechanism involving Toll-IL-1-receptor domain-containing adapter-inducing IFN-α (TRIF) and nuclear factor κB (NF-κB) causes the apoptosis of MDCC-MSB1 cells. This is the first report about the function of TLR3 in chicken T-cell lymphoma, especially in signal pathway. The mechanisms underlying TLR3-mediated apoptosis may contribute to the development of new drug to treat lymphomas and oncovirus infections.
Insights
Toll-like receptor-3 (TLR3) activation triggers apoptosis in chicken lymphoma cells. This pathway, independent of interferon, involves TRIF and NF-κB, offering potential for new lymphoma and oncovirus infection treatments.
Area of Science:
- Immunology
- Cell Biology
- Oncology
Background:
- Toll-like receptor-3 (TLR3) activates immune responses and has anti-tumor effects.
- Its role in chicken lymphoma is not well understood.
Purpose of the Study:
- To investigate the effect of TLR3 activation on Marek's disease lymphoma-derived chicken cells (MDCC-MSB1).
- To elucidate the signaling pathway involved in TLR3-mediated apoptosis in these cells.
Main Methods:
- Activation of TLR3 using poly (I:C) agonist.
- Pharmacological approaches to study the signaling pathway.
- Assessment of cell proliferation and apoptosis.
Main Results:
- Poly (I:C) activated the TLR3 pathway, inhibiting MDCC-MSB1 cell proliferation.
- TLR3 activation induced caspase-dependent apoptosis.
- An interferon-independent mechanism involving TRIF and NF-κB mediated the apoptosis.
Conclusions:
- TLR3 activation induces apoptosis in chicken T-cell lymphoma via an interferon-independent pathway.
- This finding is novel for chicken T-cell lymphoma and its signaling pathways.
- The mechanisms could inform new treatments for lymphomas and oncovirus infections.
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