NF-κB in defense and disease malian NF-κB proteins named Rel (c-Rel), RelA (p65), RelB, NF-κB1 (p50 and its precursor p105), and NF-κB2 (p52 and its precursor p100) have been described (6, 8). NF-κB/Rel proteins can exist as homoor heterodimers, and although most NF-κB dimers are activators of transcription, the p50/p50 and p52/p52 homodimers repress the transcription of their target genes (6, 8). In Drosophila, three NF-κB homologs named Dorsal, Dif, and Relish have been identified and characterized (5, 6). Structurally, all NF-κB/Rel proteins share a highly conserved NH2-terminal Rel homology domain (RHD) that is responsible for DNA binding, dimerization, and association with inhibitory proteins known as IκBs (6, 8). In resting cells, NF-κB/Rel dimers are bound to IκBs and retained in an inactive form in the cytoplasm. Like NF-κB, IκBs are also members of a multigene family containing seven known mammalian members including IκBα, IκBβ, IκBγ, IκBε, Bcl-3, the precursor Rel-proteins, p100, and p105, and one Drosophila IκB named Cactus (6, 8). The IκB family is characterized by the presence of multiple copies of ankyrin repeats, which are protein-protein interaction motifs that interact with NF-κB via the RHD. Upon appropriate stimulation, IκB is phosphorylated by IκB kinases (IKKs), polyubiquitinated by a ubiquitin ligase complex, and degraded by the 26S proteosome (6, 8). Consequently, NF-κB is released and translocates into nucleus to initiate gene expression. NF-κB regulates the expression of a wide variety of genes that play critical roles in innate immune responses (6, 7). Such NF-κB target genes include those encoding cytokines (eg, IL-1, IL-2, IL-6, IL-12, TNF-α, LTα, LTβ, and GM-CSF), adhesion molecules (eg, ICAM, VCAM, endothelial leukocyte adhesion molecule [ELAM]), acute phase proteins (eg, SAA), and inducible enzymes (eg, iNOS and COX-2)(6–8). In addition, it has been demonstrated recently that several evolutionarily conserved antimicrobial peptides, eg, β-defensins, are also regulated by NF-κB (11), a situation similar to Drosophila (2, 5). Besides regulating the expression of molecules involved in innate immunity, NF-κB also plays a role in the expression of molecules important for adaptive immunity, such as MHC proteins, and the expression of critical cytokines such as IL-2, IL-12 and IFN-γ (6). Finally NF-κB plays an important role in the overall immune response by affecting the expression of genes that are critical for regulating the apoptotic process, such as c-IAP-1 and c-IAP-2, Fas ligand, c-myc, p53, and cyclin D1 (12).