Macrophage migration inhibitory factor: A mediator of matrix metalloproteinase production

Macrophage migration inhibitory factor (MIF) is a cytokine that induces the production of a large number of proinflammatory molecules and pituitary-derived hormone, which potentiate endotoxemia. MIF has been reported to be primarily expressed in T cells and macrophages. However, recent studies have revealed this protein to be ubiquitously expressed in various cell types, and have indicated that it has more far-reaching non-immunological role(s) in a variety of pathological states. Of note, it has become evident that MIF has a broad activity on glucocorticoid-induced immunomodulation, D-dopachrometautomerase activity, and the induction of matrix metalloproteinases (MMPs). MIF plays an important role in the pathogenesis of injury, such as ultraviolet (UV)-induced damage and rheumatoid arthritis (RA). UV irradiation up-regulates the production of inflammatory cytokines, and the UV-induced increase in MMPs in dermal fibroblasts is mediated in part by MIF and IL-1β. Furthermore, MMPs are involved in tissue remodeling and may be critical to cartilage formation in RA. It is also known that MIF up-regulates the expression of MMPs 1 and 3 in the fibroblasts-like synoviocytes of patients with RA. Therefore, MIF antagonism could be a very attractive therapeutic pathway to decrease the effects of injury and RA. This chapter reviews the latest findings on the roles of MIF with regard to injury and RA.