Differential Utilization of NF-kappaB RELA and RELB in Response to Extracellular Versus Intracellular polyIC Stimulation in HT1080 Cells

BMC Immunol. 2011 Feb 10;12:15. doi: 10.1186/1471-2172-12-15.


Background: Pattern recognition receptors (PRRs) for double-stranded RNA (dsRNA) are components of innate immunity that recognize the presence of viral infection and initiate efficient defense mechanisms. In addition to previously well-characterized signaling pathways that are mediated by PKR and TLR3, new intracellular dsRNA sensors, that are members of CARD and DExD/H box helicase family, have been identified. However, the molecular mechanisms involved in the signaling pathways mediated by these new dsRNA sensors have not been extensively characterized.

Results: Here, we studied an intracellular dsRNA pathway in the human fibrosarcoma cell line HT1080, which is distinct from the TLR3-mediated extracellular dsRNA pathway. Particularly, the NF-kB subunits RELA and RELB were differentially utilized by these two dsRNA signaling pathways. In TLR3-mediated dsRNA signaling, siRNA knock-down studies suggested a limited role for RELA on regulation of interferon beta and other cytokines whereas RELB appeared to have a negative regulatory role. By contrast, intracellular dsRNA signaling was dependent on RELA, but not RELB.

Conclusions: Our study suggests that extracellular and intracellular dsRNA signaling pathways may utilize different NF-kB members, and particularly the differential utilization of RELB may be a key mechanism for powerful inductions of NF-kB regulated genes in the intracellular dsRNA signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cytokines / genetics
  • Cytokines / metabolism
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • I-kappa B Kinase / antagonists & inhibitors
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism
  • Interferon-beta / genetics
  • Interferon-beta / metabolism
  • Poly I-C / genetics*
  • Poly I-C / metabolism
  • Poly I-C / pharmacology
  • RNA Interference
  • RNA, Double-Stranded / genetics
  • RNA, Double-Stranded / metabolism
  • Receptors, Pattern Recognition / genetics
  • Receptors, Pattern Recognition / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics*
  • Toll-Like Receptor 3 / genetics
  • Toll-Like Receptor 3 / metabolism
  • Transcription Factor RelA / genetics*
  • Transcription Factor RelA / metabolism
  • Transcription Factor RelB / genetics*
  • Transcription Factor RelB / metabolism
  • Transfection


  • Cytokines
  • Enzyme Inhibitors
  • RELB protein, human
  • RNA, Double-Stranded
  • Receptors, Pattern Recognition
  • Toll-Like Receptor 3
  • Transcription Factor RelA
  • Transcription Factor RelB
  • Interferon-beta
  • I-kappa B Kinase
  • Poly I-C