Heme oxygenase-1 as a target for the design of gene and pharmaceutical therapies for autoimmune diseases.
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.
Juan P
JP
Mackern-Oberti
Sebastian A
SA
Riquelme
Carolina
C
Llanos
Camila B
CB
Schmidt
Thomas
T
Simon
Ignacio
I
Anegon
Evelyn
E
Jara
Claudia A
CA
Riedel
Susan M
SM
Bueno
Millennium Institute on Immunology and Immunotherapy Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Departamento de Inmunología Clínica y Reumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile. Av Portugal #49, Santiago, Chile. akalergis@bio.puc.cl.
Alexis M
AM
Kalergis
D000818:Animals; D001327:Autoimmune Diseases / Q000201:enzymology* / Q000628:therapy*; D002248:Carbon Monoxide / Q000008:administration & dosage*; D002470:Cell Survival; D004195:Disease Models, Animal; D018390:Gene Targeting / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans
D002248:Carbon Monoxide; D051547:Heme Oxygenase-1