Calcineurin subunit B upregulates β-interferon production by phosphorylation of interferon regulatory factor 3 via Toll-like receptor 4

Cancer Sci. 2012 Mar;103(3):515-21. doi: 10.1111/j.1349-7006.2011.02160.x. Epub 2012 Jan 6.

Abstract

Toll-like receptors (TLRs) function as pattern-reorganization receptors in mammals and play an essential role in innate immunity. After recognizing certain ligands, TLRs activate a cascade of signal pathways to establish a guard environment. For the first time, we report that in vitro treatment with recombinant calcineurin subunit B (CNB) upregulated several TLR-related genes. Calcineurin subunit B interacted with the ectodomain of TLR4 in vitro. On further investigation, phosphorylation of interferon regulatory factor 3 and degradation of IκB-α were observed by CNB stimulation. In addition to pro-inflammatory cytokines, transcription and production of β-interferon were also enhanced after CNB stimulation. Thus, CNB could be further explored as a cancer and virus immunotherapy drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Calcineurin / immunology
  • Calcineurin / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation / immunology*
  • Immunity, Innate / immunology
  • Interferon Regulatory Factor-3 / immunology
  • Interferon Regulatory Factor-3 / metabolism*
  • Interferon-beta / biosynthesis*
  • Interferon-beta / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Oligonucleotide Array Sequence Analysis
  • Phosphorylation
  • Real-Time Polymerase Chain Reaction
  • Toll-Like Receptor 4 / immunology
  • Toll-Like Receptor 4 / metabolism*
  • Up-Regulation

Substances

  • Interferon Regulatory Factor-3
  • Toll-Like Receptor 4
  • Interferon-beta
  • Calcineurin