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Pre‐B cell colony‐enhancing factor (PBEF)/visfatin: a novel mediator of innate immunity
Author(s) -
Luk Tracy,
Malam Zeenat,
Marshall John C.
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0807581
Subject(s) - biology , mediator , innate immune system , inflammation , immunology , nad+ kinase , sirtuin 1 , microbiology and biotechnology , immunity , immune system , biochemistry , downregulation and upregulation , enzyme , gene
Pre‐B cell colony‐enhancing factor (PBEF), also known as visfatin, is a highly conserved, 52‐kDa protein found in living species from bacteria to humans. Originally a curiosity identified serendipitously in microarray studies but having no obvious functional importance, PBEF has now been shown to exert three distinct activities of central importance to cellular energetics and innate immunity. Within the cell, PBEF functions as a nicotinamide phosphoribosyl transferase, the rate‐limiting step in a salvage pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis. By virtue of this role, it can regulate cellular levels of NAD and so impact not only cellular energetics but also NAD‐dependent enzymes such as sirtuins. Although it lacks a signal peptide, PBEF is released by a variety of cells, and elevated levels can be found in the systemic circulation of patients with a variety of inflammatory diseases. As an extracellular cytokine, PBEF can induce the cellular expression of inflammatory cytokines such as TNF‐α, IL‐1β, and IL‐6. Finally, PBEF has been shown to be an adipokine expressed by fat cells that exerts a number of insulin mimetic and antagonistic effects. PBEF expression is up‐regulated in a variety of acute and chronic inflammatory diseases including sepsis, acute lung injury, rheumatoid arthritis, inflammatory bowel disease, and myocardial infarction and plays a key role in the persistence of inflammation through its capacity to inhibit neutrophil apoptosis. This review summarizes the admittedly incomplete body of emerging knowledge about a remarkable new mediator of innate immunity.