Role of NF-κB Activation in Macrophages

Abstract

Nuclear factor-κB (NF-κB) is the prototypical pro-inflammatory transcription factor, this is primarily based on its activation by pro-inflammatory cytokines such as interleukin 1 (IL-1) and tumor necrosis factor α (TNFα), and pattern recognition receptors (PRRs) including Toll-like receptors (TLRs). In response to these pro-inflammatory signals NF-κB regulates the expression of other pro-inflammatory and cell survival genes that perpetuate the inflammatory response. It is this pivotal role in pro-inflammatory signaling pathways that has attracted a great deal of interest in NF-κB as a therapeutic target in inflammatory and autoimmune diseases. In light of their important role in orchestrating inflammation and immunity, NF-κB activation in macrophages has long been thought to be a major factor in the inflammatory response and consequently many inflammation-associated diseases. However, in recent years the development of sophisticated genetic tools to study the cell-specific role of the NF-κB in vivo has revealed previously unexpected anti-inflammatory and immunosuppressive roles for this pathway specifically in the macrophage lineage. In this chapter we will review these recent insights into the role of NF-κB activation in macrophages and related myeloid cells in the context of inflammation and immunity.