The complicated path to true causes of disease: role of nuclear factor B in inflammatory bowel disease

Challenging our understanding of the role of nuclear factor κB activation in the pathophysiology of intestinal inflammation in human inflammatory bowel disease Nuclear factor kappa B (NFκB) was discovered as a transcription factor some 15 years ago.1 Since then the protein has been linked to early pathophysiological events in a host of inflammatory conditions. NFκB, in most instances, is a heterodimer composed of a p50 and p65 subunit. In most mammalian cells NFκB is found in the resting state in the cytoplasm where it is bound in a complex to a protein that is a member of a family of specific inhibitors (IKK). Following phosphorylation, the inhibitor is rapidly degraded and the released NFκB migrates within minutes into the nucleus where it can specifically induce gene expression by binding to sequence defined DNA elements in gene promoter regions. Even after more than a decade of mechanistic and clinical studies, the role of NFκB in intestinal inflammation is not fully …