Differential utilization of NF-kappaB RELA and RELB in response to extracellular versus intracellular polyIC stimulation in HT1080 cells

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.

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.

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.