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

Manabu Taura, Ayaka Eguma, Mary Ann Suico, Tsuyoshi Shuto, Tomoaki Koga, Kensei Komatsu, Takefumi Komune, Takashi Sato, Hideyuki Saya, Jian Dong Li, Hirofumi Kai

Research output: Contribution to journalArticle

78 Citations (Scopus)

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 IκB-α, nuclear translocation of NF-κB, 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.

Original languageEnglish
Pages (from-to)6557-6567
Number of pages11
JournalMolecular and Cellular Biology
Volume28
Issue number21
DOIs
Publication statusPublished - 2008 Nov

Fingerprint

Toll-Like Receptor 3
HCT116 Cells
Epithelial Cells
Cell Line
Toll-Like Receptors
Innate Immunity
Interferon Regulatory Factor-3
Phosphorylation
Transcription Factor 3
Messenger RNA
Double-Stranded RNA
Interferon-beta
Viral RNA
Interleukin-8
Fluorouracil
Small Interfering RNA
Intestines
Signal Transduction
Liver
polyriboinosinic-polyribocytidylic acid

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Taura, M., Eguma, A., Suico, M. A., Shuto, T., Koga, T., Komatsu, K., ... Kai, H. (2008). p53 regulates toll-like receptor 3 expression and function in human epithelial cell lines. Molecular and Cellular Biology, 28(21), 6557-6567. https://doi.org/10.1128/MCB.01202-08

p53 regulates toll-like receptor 3 expression and function in human epithelial cell lines. / Taura, Manabu; Eguma, Ayaka; Suico, Mary Ann; Shuto, Tsuyoshi; Koga, Tomoaki; Komatsu, Kensei; Komune, Takefumi; Sato, Takashi; Saya, Hideyuki; Li, Jian Dong; Kai, Hirofumi.

In: Molecular and Cellular Biology, Vol. 28, No. 21, 11.2008, p. 6557-6567.

Research output: Contribution to journalArticle

Taura, M, Eguma, A, Suico, MA, Shuto, T, Koga, T, Komatsu, K, Komune, T, Sato, T, Saya, H, Li, JD & Kai, H 2008, 'p53 regulates toll-like receptor 3 expression and function in human epithelial cell lines', Molecular and Cellular Biology, vol. 28, no. 21, pp. 6557-6567. https://doi.org/10.1128/MCB.01202-08
Taura, Manabu ; Eguma, Ayaka ; Suico, Mary Ann ; Shuto, Tsuyoshi ; Koga, Tomoaki ; Komatsu, Kensei ; Komune, Takefumi ; Sato, Takashi ; Saya, Hideyuki ; Li, Jian Dong ; Kai, Hirofumi. / p53 regulates toll-like receptor 3 expression and function in human epithelial cell lines. In: Molecular and Cellular Biology. 2008 ; Vol. 28, No. 21. pp. 6557-6567.
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