Heme Oxygenase-1 as a Target for the Design of Gene and Pharmaceutical Therapies for Autoimmune Diseases
Juan P. Mackern-Oberti,
Sebastian A. Riquelme,
Camila B. Schmidt,
Claudia A. Riedel,
Susan M. Bueno,
Alexis M. Kalergis.
One of the major goals in the research of autoimmune diseases is to develop specific therapies to regulate the
expression and function of gene products that could contribute to restoring tolerance to self-constituents and replace conventional
systemic immunosuppression, which is associated with important undesired side effects. Although significant
progress has been made on the understanding of the pathogenesis of autoimmunity, therapies for these ailments have not
seen a change. During the last decade, different strategies such as pharmacologic or gene therapy modulation of heme
oxygenase-1 (HO-1) and the administration of its metabolic product, carbon monoxide (CO), have been shown to display
beneficial immunoregulatory and cytoprotective properties. In different experimental autoimmune conditions, such as Experimental
autoimmune encephalomyelitis, type-1 diabetes and systemic lupus erythematosus, genetic or pharmacological
modulation of HO-1, as well as delivery of CO have shown to ameliorate disease progression. Furthermore, it has been
demonstrated that dendritic cell and monocyte function can be modulated by HO-1 and/or CO. In this article, recent data
related to the immunoregulatory properties of HO-1/CO will be discussed, focusing on their potential therapeutic use to
treat autoimmune diseases.
Keywords: Heme oxygenase-1, carbon monoxide, autoimmunity, tolerance, therapy.
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