NF-κB

Abstract

Nuclear factor (NF)-κB was first described in 1986 by the group of Nobel Prize winner David Baltimore as a nuclear factor necessary for immunoglobulin κ light chain transcription [1, 2]. It exists in virtually all known cell types and mitochondria [3, 4] and regulates the transcription of an exceptionally large number of genes, including those involved in immune and inflammatory response, cell death, and proliferation [5]. In the last few years, tremendous progress has been made in advancing our understanding of the complex functions of this pathway in vivo. In particular, studies using conditional knockout technology in mice to specifically inactivate this pathway in certain tissues have highlighted the crucial function of NF-κB in linking innate immune responses and cytokine signaling to all kinds of pathological conditions that had not initially been associated with inflammation [6]. As the liver is a preferred source of and target for cytokines, it is not surprising that the NF-κB pathway influences nearly all physiological processes in the liver and hepatic diseases such as acute liver failure, hepatocarcinogenesis, and hepatic fibrogenesis [7]. On the basis of its fundamental importance, it is more than likely that novel molecular therapies targeting members of the NF-κB pathway will be developed in the near future and will enter daily clinical practice. Therefore, to understand the basic principles of this pathway, we will give a short introduction to the structure and basic activation pathways of NF-κB, describe its role in modulating hepatocyte cell death, and then focus on its role in hepatic disease conditions, namely hepatocarcinogenesis, liver fibrosis, and hepatitis. © 2010 Springer-Verlag Berlin Heidelberg.