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Cited by 129Immune Response and InflammationCancer-related Molecular Pathwaysinterferon and immune responses

p53 regulates Toll-like receptor 3 expression and function in human epithelial cell lines

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Taura, Manabu, Eguma, Ayaka, Suico, Mary Ann, Shuto, Tsuyoshi, Koga, Tomoaki, Komatsu, Kensei, Komune, Takefumi, Sato, Takashi +3 more·2008·Molecular and Cellular Biology
DOI 10.1128/mcb.01202-08PMC PMC2573237
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Abstract

Toll-like receptors (TLRs) are important sensors of microbial pathogens and mediators of innate immune responses. Although the signal transduction of TLRs is well elucidated, their basal regulation is largely unexplored. Here we show that the tumor suppressor p53 positively regulates the transcription of TLR3, a receptor for viral double-stranded RNA and poly(I-C), by binding to the p53 site in the TLR3 promoter. TLR3 expression was lower in HCT116 p53(-/-) cells than in HCT116 p53(+/+) cells. Activation of p53 by 5-fluorouracil increased the TLR3 mRNA in epithelial cell lines with wild-type p53 but not in cell lines harboring mutant p53. Knockdown of p53 by small interfering RNA decreased the TLR3 expression. TLR3 mRNA was also lower in liver and intestine of p53(-/-) mice than in p53(+/+) mice. Furthermore, the poly(I-C)-induced phosphorylation of IkappaB-alpha, nuclear translocation of NF-kappaB, and phosphorylation of interferon regulatory transcription factor 3, were drastically reduced in HCT116 p53(-/-) cells, indicating a dysregulation of the two signaling pathways governed by TLR3. Consequently, induction of interleukin-8 and beta interferon after poly(I-C) stimulation was impaired in HCT116 p53(-/-) cells. These results suggest that p53 influences TLR3 expression and function and highlight a role of p53 in innate immune response in epithelial cells.

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  • Wild type p53 (WT p53) can regulate expression of most innate immune-related Toll-like-receptor genes (TLRs) in human cells, thereby affecting immune responses.

    “We previously found that wild type p53 (WT p53) can regulate expression of most innate immune-related Toll-like-receptor genes (TLRs) in human cells, thereby affecting immune responses.”

    From Ligand dependent restoration of human TLR3 signaling and death in p53 mutant cells (2016) · cites this paper as [23]

    The Results and Discussion show that p53 regulates TLR3 expression in human epithelial cells and affects downstream cytokine responses. The Discussion mentions only preliminary evidence for TLR7 and TLR8 regulation and does not establish regulation of most TLR genes. No page numbers were supplied for these passages. (LLM, conf=0.90)

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  • P151H and R337H positively regulated TLR3 expression in a luciferase reporter assay using the TLR3 promoter region.

    “We also confirmed that P151H and R337H positively regulated TLR3 expression in a luciferase reporter assay using the promoter region of TLR3, which contains a validated binding site for p53 [23].”

    From Ligand dependent restoration of human TLR3 signaling and death in p53 mutant cells (2016) · cites this paper as [23]

  • In HCT116 p53 null cells, basal TLR3 levels are 50% less than in HCT116 p53+/+ cells.

    “In HCT116 p53 null cells the basal levels of TLR3 are 50% less than in the HCT116 p53+/+ cells [23].”

    From Ligand dependent restoration of human TLR3 signaling and death in p53 mutant cells (2016) · cites this paper as [23]

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Cited by

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Authors
Taura, M., Eguma, A., Suico, M. A., Shuto, T., Koga, T., Komatsu, K., Komune, T., Sato, T., Saya, H., Li, J.-D., & Kai, H.
Affiliations
  • Kumamoto University (JP)
  • Keio University (JP)
  • Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York 14642
Corresponding author
Kai, Hirofumi
ORCID
Venue
Molecular and Cellular Biology
Publisher
Informa UK Limited
Published
2008-11-01
Volume
28
Issue
21
Pages
6557-6567
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
DOI
10.1128/mcb.01202-08
PMC
PMC2573237
OpenAlex
W2144640444
Cited by
129
References
5
Citations by year
2026: 1 · 2025: 7 · 2024: 6 · 2023: 7 · 2022: 4 · 2021: 7 · 2020: 5 · 2019: 7 · 2018: 8 · 2017: 9 · 2016: 12 · 2015: 10 · 2014: 12 · 2013: 10 · 2012: 7
FWCI
2.37
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Johns Hopkins University (HCT116)
  • Ministry of Education, Culture, Sports, Science and Technology
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords
p53, TLR3, p53 binding sites, p53 knockout mice, epithelial cells, innate immunity, double-stranded RNA sensing, poly(I:C), NF-κB signaling, IRF3, IκBα phosphorylation, interleukin-8, interferon-beta, 5-fluorouracil, HCT116 cells
MeSH terms
Animals, Epithelial Cells, Humans, Intestinal Mucosa, Liver, Poly I-C, Promoter Regions, Genetic, Protein Binding, RNA, Messenger, Signal Transduction, Transcriptional Activation, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53, Cytokines, Cell Line, Tumor, Toll-Like Receptor 3, Mice

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