Cutting edge : synchronization of IRF1, JunB, and C/EBP activities during TLR3-TLR7 cross-talk orchestrates timely cytokine synergy in the proinflammatory response
Multiple pathogen-associated molecular pattern–induced TLR pathway cross-talk provokes proinflammatory cytokine synergy in macrophages, which is important for pathogen resistance and immune homeostasis. However, the detailed mechanisms are unclear. In this article, we demonstrate viral RNA analog–in...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2015
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| Online Access: | https://hdl.handle.net/10356/97885 http://hdl.handle.net/10220/38510 |
| _version_ | 1824455649958821888 |
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| author | Yong, Wai Khang Sze, Newman Siu Kwan Tan, Nguan Soon Liu, Qian Zhu, Yong Ding, Jeak Ling |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Yong, Wai Khang Sze, Newman Siu Kwan Tan, Nguan Soon Liu, Qian Zhu, Yong Ding, Jeak Ling |
| author_sort | Yong, Wai Khang |
| collection | NTU |
| description | Multiple pathogen-associated molecular pattern–induced TLR pathway cross-talk provokes proinflammatory cytokine synergy in macrophages, which is important for pathogen resistance and immune homeostasis. However, the detailed mechanisms are unclear. In this article, we demonstrate viral RNA analog–induced transcription synergy of Il6 and Il12b via IFN regulatory factor (IRF)1 (TLR3–TIR domain–containing adaptor inducing IFN-β [TRIF] responsive), C/EBPβ (TLR7-MyD88 responsive), and JunB (all responsive). Coactivation of the TLR3 and TLR7 pathways synchronizes the interaction of IRF1, JunB, and C/EBPβ with the Il6 and Il12b promoters, facilitating maximal gene expression. MyD88 pathway activation suppresses TRIF-induced IRF1 in a delayed manner, controlling the magnitude and timing of cytokine expression. Our findings provide novel mechanisms of cooperation of different TLR pathways to achieve optimal immune responses, with the potential for immunomodulatory strategies. |
| first_indexed | 2025-02-19T03:41:34Z |
| format | Journal Article |
| id | ntu-10356/97885 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:41:34Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/978852022-02-16T16:29:53Z Cutting edge : synchronization of IRF1, JunB, and C/EBP activities during TLR3-TLR7 cross-talk orchestrates timely cytokine synergy in the proinflammatory response Yong, Wai Khang Sze, Newman Siu Kwan Tan, Nguan Soon Liu, Qian Zhu, Yong Ding, Jeak Ling School of Biological Sciences DRNTU::Science::Biological sciences::Microbiology::Bacteria Multiple pathogen-associated molecular pattern–induced TLR pathway cross-talk provokes proinflammatory cytokine synergy in macrophages, which is important for pathogen resistance and immune homeostasis. However, the detailed mechanisms are unclear. In this article, we demonstrate viral RNA analog–induced transcription synergy of Il6 and Il12b via IFN regulatory factor (IRF)1 (TLR3–TIR domain–containing adaptor inducing IFN-β [TRIF] responsive), C/EBPβ (TLR7-MyD88 responsive), and JunB (all responsive). Coactivation of the TLR3 and TLR7 pathways synchronizes the interaction of IRF1, JunB, and C/EBPβ with the Il6 and Il12b promoters, facilitating maximal gene expression. MyD88 pathway activation suppresses TRIF-induced IRF1 in a delayed manner, controlling the magnitude and timing of cytokine expression. Our findings provide novel mechanisms of cooperation of different TLR pathways to achieve optimal immune responses, with the potential for immunomodulatory strategies. 2015-08-24T09:05:55Z 2019-12-06T19:47:40Z 2015-08-24T09:05:55Z 2019-12-06T19:47:40Z 2015 2015 Journal Article Liu, Q., Zhu, Y., Yong, W. K., Sze, N. S. K., Tan, N. S., & Ding, J. L. (2015). Cutting edge : synchronization of IRF1, JunB, and C/EBP activities during TLR3-TLR7 cross-talk orchestrates timely cytokine synergy in the proinflammatory response. The Journal of Immunology, 195(3), 801-805. https://hdl.handle.net/10356/97885 http://hdl.handle.net/10220/38510 10.4049/jimmunol.1402358 26109639 en The journal of immunology © 2015 The American Association of Immunologists. |
| spellingShingle | DRNTU::Science::Biological sciences::Microbiology::Bacteria Yong, Wai Khang Sze, Newman Siu Kwan Tan, Nguan Soon Liu, Qian Zhu, Yong Ding, Jeak Ling Cutting edge : synchronization of IRF1, JunB, and C/EBP activities during TLR3-TLR7 cross-talk orchestrates timely cytokine synergy in the proinflammatory response |
| title | Cutting edge : synchronization of IRF1, JunB, and C/EBP activities during TLR3-TLR7 cross-talk orchestrates timely cytokine synergy in the proinflammatory response |
| title_full | Cutting edge : synchronization of IRF1, JunB, and C/EBP activities during TLR3-TLR7 cross-talk orchestrates timely cytokine synergy in the proinflammatory response |
| title_fullStr | Cutting edge : synchronization of IRF1, JunB, and C/EBP activities during TLR3-TLR7 cross-talk orchestrates timely cytokine synergy in the proinflammatory response |
| title_full_unstemmed | Cutting edge : synchronization of IRF1, JunB, and C/EBP activities during TLR3-TLR7 cross-talk orchestrates timely cytokine synergy in the proinflammatory response |
| title_short | Cutting edge : synchronization of IRF1, JunB, and C/EBP activities during TLR3-TLR7 cross-talk orchestrates timely cytokine synergy in the proinflammatory response |
| title_sort | cutting edge synchronization of irf1 junb and c ebp activities during tlr3 tlr7 cross talk orchestrates timely cytokine synergy in the proinflammatory response |
| topic | DRNTU::Science::Biological sciences::Microbiology::Bacteria |
| url | https://hdl.handle.net/10356/97885 http://hdl.handle.net/10220/38510 |
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