NF-κB and the regulation of hematopoiesis

Abstract

This review will focus on the role of nuclear factor jB (NF-jB) signaling in hematopoietic differentiation. We will also discuss several hematopoietic pathologies associated with deregulation of NF-jB and their potential therapies.

PU.1 and C/EBPα synergistically program distinct response to NF-κB activation through establishing monocyte specific enhancers

“…For example, in THP-1 cells, many genes involved in hematopoiesis are up-regulated upon TNF-α treatment (Fig. 1B), which is consistent with the known origin of THP-1 cells and function of NF-κB in regulating hematopoietic lineage differentiation (15). Database deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no.…”

Experimental Stroke-Induced Changes in the Bone Marrow Reveal Complex Regulation of Leukocyte Responses

“…We evaluated whether experimental stroke led to the activation of leukocytes in the bone marrow, by assessing NFkB and p38 MAPK, two common signalling pathways in various haematopoietic cells (Bottero et al, 2006;Geest and Coffer, 2009). Western blotting identified rapid induction of NFkB p65 in the bone marrow after stroke at 10 minutes reperfusion (70 minutes onset of ischaemia), which was further augmented by 4 hours (Figure 2A).…”

Mutual cross-talk between reactive oxygen species and nuclear factor-kappa B: molecular basis and biological significance

“…The prosurvival activity of NF-kB also plays a key role in a wide range of other biological processes, including maturation of B and T lymphocytes (Hayden and Ghosh, 2004;Bottero et al, 2006;Claudio et al, 2006), innate and adaptive immunity (Weil and Israe¨l, 2006), bone morphogenesis epidermal homeostasis, hair follicle development, and neuronal development and function (Kucharczak et al, 2003;Mattson and Meffert, 2006). When deregulated, NF-kB-mediated suppression of PCD also participates in the pathogenesis of widespread human diseases, including various cancers -where it promotes transformation, tumor progression and resistance to anticancer therapy (Brasseres and Baldwin, 2006;Dutta et al, 2006; see also Kucharczak et al, 2003;Karin, 2006;Kim et al, 2006) -chronic inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), various inherited conditions, and metabolic and vascular disorders such as type-II diabetes and atherosclerosis (Kucharczak et al, 2003;Kumar et al, 2004;Courtois and Smahi, 2006;Perkins and Gilmore, 2006).…”

“…The different aspects of the regulation and functions of NF-kB-family transcription factors and their role in control of PCD are the subject of other articles in this issue (Dutta et al, 2006;Gilmore, 2006;Perkins, 2006;Scheidereit, 2006) and of excellent reviews previously published elsewhere (Gerondakis and Strasser, 2003;Kucharczak et al, 2003;Hayden and Ghosh, 2004;Bottero et al, 2006;Claudio et al, 2006;Courtois and Smahi, 2006;Karin, 2006;Kim et al, 2006;Mattson and Meffert, 2006;Perkins and Gilmore, 2006) Here, we focus on recent discoveries that have unveiled how NF-kB and ROS engage in a mutual cross-talk. Specifically, we discuss the status of our current understanding of the basis for involvement of ROS in activation of NF-kB, and the mechanisms underlying the negative control that NF-kB exerts on these species and, ultimately, PCD.…”

“…This negative control that NF-kB exerts on ROS formation appears to be especially crucial for the suppression of PCD induced by the proinflammatory cytokine tumor necrosis factor (TNF)a and perhaps other stimuli (Sakon et al, 2003;Pham et al, 2004;Kamata et al, 2005;Papa et al, 2006). In addition to antagonism of TNFa-induced PCD, the prosurvival action of NF-kB is essential for B and T lymphopoiesis, bone morphogenesis and pathogenesis of widespread human diseases, ranging from cancer and chronic inflammation to vascular and metabolic disorders (Kucharczak et al, 2003;Greten and Karin, 2004;Kumar et al, 2004;Bottero et al, 2006;Courtois and Smahi, 2006;Karin, 2006;Kim et al, 2006;Papa et al, 2006). Thus, ROS appear to be at an obligatory crossroads of opposing pathways for life and death elicited by the engagement of TNF receptors (TNF-Rs) and, most likely, other triggers.…”