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

研究成果: Article査読

85 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)6557-6567
ページ数11
ジャーナルMolecular and Cellular Biology
28
21
DOI
出版ステータスPublished - 11-2008
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 細胞生物学

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