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Macrophage migration inhibitory factor (MIF) is a pro-inflammatory mediator with the ability to induce various immunomodulatory responses and override glucocorticoid-driven immunosuppression. Some of these functions have been linked to the unusual enzymatic properties of the protein, namely tautomerase and oxidoreductase activities. However, there are conflicting reports regarding the functional role of these enzymatic properties in normal physiological homeostasis and disease progression. Therefore, we have produced a highly pure, virtually endotoxin-free recombinant MIF preparation and fully characterized this using a variety of biochemical and biophysical approaches. The recombinant protein, with demonstrable enzymatic activity, was then used to systematically examine the biological activity of MIF. Surprisingly, treatment with MIF alone failed to induce cytokine expression, with the exception of IL-8. However, co-treatment of lipopolysaccharide (LPS) in conjunction with MIF produced synergistic secretion of tumor necrosis factor-alpha, interleukin (IL)-1, and IL-8 compared with LPS alone. The potentiating effect of MIF was seen at physiologically relevant concentrations. These data suggest that MIF has no conventional cytokine activity but, rather, acts to modulate and amplify the response to LPS.

Original publication

DOI

10.1074/jbc.M601103200

Type

Journal article

Journal

J Biol Chem

Publication Date

06/10/2006

Volume

281

Pages

29641 - 29651

Keywords

Animals, Cell Line, Cell Movement, Cell Survival, Cytokines, Drug Synergism, Granulocytes, Humans, Inflammation Mediators, Leukocytes, Mononuclear, Lipopolysaccharides, Macrophage Migration-Inhibitory Factors, Rats, Recombinant Proteins