DNA vaccination against macrophage migration inhibitory factor improves atopic dermatitis in murine models.
ABSTRACT Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that has been implicated in the pathogenesis of AD. Recently, we developed a novel DNA vaccine that generates neutralizing endogenous anti-MIF antibodies.
This study explores the preventive and therapeutic effects of this MIF-DNA vaccine in mouse models of AD.
Two different AD model mice (DS-Nh and NC/Nga) received MIF-DNA vaccination to analyze preventive and therapeutic effects, as assessed by clinical skin scores, histologic findings, and serum IgE levels.
In murine models of AD, MIF-DNA vaccination prevented the occurrence of the AD skin phenotype. Furthermore, administration of MIF-DNA vaccine to mice that had already developed AD produced a rapid improvement in AD skin manifestation. There were reduced histologic signs of inflammation and lower serum IgE levels in treated mice compared with those seen in control animals. Finally, passive transfer of IgG from MIF-DNA vaccinated mice to AD mice also produced a significant therapeutic effect. These results demonstrate that MIF-DNA vaccination not only prevents the development of AD but also improves the symptoms of pre-existing AD.
Taken together, the induction of an anti-MIF autoantibody response using MIF-DNA vaccination appears to be a useful approach in the treatment of AD.
Article: The Role of Macrophage Migration Inhibitory Factor (MIF) in Ultraviolet Radiation-Induced Carcinogenesis[show abstract] [hide abstract]
ABSTRACT: Ultraviolet (UV) radiation is the most common cause of physical injury to the skin due to environmental damage, and UV exposure substantially increases the risk of actinic damage to the skin. The inflammatory changes induced by acute UV exposure include erythema (sunburn) of the skin, while chronic exposure to solar UV radiation causes photo-aging, immunosuppression, and ultimately, carcinogenesis of the skin. After skin damage by UV radiation, the cells are known to secrete many cytokines, including interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α. and macrophage migration inhibitory factor (MIF). MIF was originally identified as a lymphokine that concentrates macrophages at inflammatory loci, and is known to be a potent activator of macrophages in vivo. MIF is considered to play an important role in cell-mediated immunity. Since the molecular cloning of MIF cDNA, MIF has been re-evaluated as a proinflammatory cytokine and pituitary-derived hormone that potentiates endotoxemia. MIF is ubiquitously expressed in various tissues, including the skin. Recent studies have suggested a potentially broader role for MIF in growth regulation because of its ability to antagonize p53-mediated gene activation and apoptosis. This article reviews the latest findings on the roles of MIF with regard to UV-induced skin cancer.Cancers. 01/2010;