Title |
Rb/E2F1 Regulates the Innate Immune Receptor Toll-Like Receptor 3 in Epithelial Cells
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Published in |
Molecular & Cellular Biology, March 2023
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DOI | 10.1128/mcb.06454-11 |
Pubmed ID | |
Authors |
Manabu Taura, Mary Ann Suico, Kosuke Koyama, Kensei Komatsu, Rui Miyakita, Chizuru Matsumoto, Eriko Kudo, Ryusho Kariya, Hiroki Goto, Shunsuke Kitajima, Chiaki Takahashi, Tsuyoshi Shuto, Mitsuyoshi Nakao, Seiji Okada, Hirofumi Kai |
Abstract |
Tumor suppressor genes regulate the antiviral host defense through molecular mechanisms that are not yet well explored. Here, we show that the tumor suppressor retinoblastoma (Rb) protein positively regulates Toll-like receptor 3 (TLR3) expression, the sensing receptor for viral double-stranded RNA and poly(I · C). TLR3 expression was lower in Rb knockout (Rb(-/-)) mouse embryonic fibroblasts (MEF) and in mammalian epithelial cells transfected with Rb small-interfering RNA (siRNA) than in control cells. Consequently, induction of cytokines interleukin-8 and beta interferon after poly(I · C) stimulation was impaired in Rb(-/-) MEF and Rb siRNA-transfected cells compared to controls. TLR3 promoter analysis showed that Rb modulates the transcription factor E2F1, which directly binds to the proximal promoter of TLR3. Exogenous addition of E2F1 decreased TLR3 promoter activity, while Rb dose dependently curbed the effect of E2F1. Interestingly, poly(I · C) increased the Rb expression, and the poly(I · C)-induced TLR3 expression was impaired in Rb-depleted cells, suggesting the importance of Rb in TLR3 induction by poly(I · C). Together, these data indicated that E2F1 suppresses TLR3 transcription, but during immune stimulation, Rb is upregulated to block the inhibitory effect of E2F1 on TLR3, highlighting a role of Rb-E2F1 axis in the innate immune response in epithelial cells. |
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United States | 1 | 100% |
Demographic breakdown
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
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India | 1 | 3% |
Austria | 1 | 3% |
Unknown | 34 | 92% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 10 | 27% |
Student > Ph. D. Student | 8 | 22% |
Professor > Associate Professor | 5 | 14% |
Student > Master | 4 | 11% |
Student > Doctoral Student | 1 | 3% |
Other | 2 | 5% |
Unknown | 7 | 19% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 6 | 16% |
Medicine and Dentistry | 4 | 11% |
Social Sciences | 2 | 5% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 5% |
Other | 0 | 0% |
Unknown | 7 | 19% |