D-Dopachrome tautomerase (D-DT) : functional homologue or cross-regulator of macrophage migration inhibitory factor (MIF)?

TL;DRAbstract

Macrophage migration inhibitory factor (MIF) is a pleiotropic immunoregulatory and pro-inflammatory cytokine, which plays a pivotal role in the pathogenesis of various acute and chronic inflammatory diseases. For example, endotoxemia studies in mice reveal that MIF administration decreases the survival rate, whereas MIF neutralization or genetic deletion of Mif improve the chances for a beneficial outcome. Additionally, high MIF levels are measured in a variety of human tumors and functional studies reveal MIF involvement in multiple aspects of tumor progression including control of cell proliferation and prevention of apoptosis. Unlike other cytokines, MIF also is a phenylpyruvate tautomerase that converts two non-physiologic enzymatic substrates, D-dopachrome and p-hydroxyphenylpyruvate (HPP). To date, possible relationships between the tautomerase and inflammatory or tumor-supportive activities of MIF remain unclear. In 1993, D-dopachrome tautomerase (D-DT) was discovered during an

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