Pre-B cell colony enhancing factor (PBEF), a cytokine with multiple physiological functions

Abstract

Pre-B cell colony enhancing factor (PBEF) is regarded as a proinflammatory cytokine. Named for its first discovered function as a pre-B cell colony enhancing factor, it has since been found to have many other functions relating to cell metabolism, inflammation, and immune modulation. It has also been found to have intracellular and extracellular forms, with the two overlapping in function. Most of the intracellular functions of PBEF are due to its role as a nicotinamide phosphoribosyltransferase (Nampt). It has been found in human endothelial cells, where it is able to induce angiogenesis through upregulation of VEGF and VEGFR and secretion of MCP-1. In human umbilical endothelial cells, PBEF increases levels of the protease MMP 2/9. PBEF has also been found in a variety of immune cells other than B cells and has been shown to inhibit apoptosis of macrophages. Extracellular PBEF has been shown to increase inflammatory cytokines, such as TNF-α, IL-1β, IL-16, and TGF-β1, and the chemokine receptor CCR3. PBEF also increases the production of IL-6, TNF-α, and IL-1β in CD14(+) monocyctes, macrophages, and dendritic cells, enhances the effectiveness of T cells, and is vital to the development of both B and T lymphocytes. The purpose of this review is to summarize the recent advances in PBEF research.

Keywords: B lymphocyte; Chemokine; Monocyte; Pre-B cell enhancing factor; T lymphocyte.

Figure 1

PBEF stimulates expression and release of other cytokines. PBEF, pre-B-Cell colony enhancing factor; IL, interleukin, TGF-β1, transforming growth factor-1β; TNF-α, tumor necrosis factor-α; NFkB, nuclear factor kB; STAT3, signal transducer and activator of transcription 3; CCR-3, C-C chemokine receptor type 2;

Figure 2

PBEF activates T cells, B cells and monocytes. PI3K, phosphoinosite 3-kinase; TNF-α, tumor necrosis factor-α; MCP-1, monocyte chemotactic protein-1.

Figure 3

PBEF is involved in the pathogenesis of several diseases. MCP-1, monocyte chemotactic protein-1; CCR-2, C-C chemokine receptor type 2; PI3K, phosphoinosite 3-kinase; MEK1/2; mitogen-activated protein kinase kinase 1/2