RESUMO
The aetiology and progression of systemic lupus erythematosus (SLE) resulted from a complex sequence of events generated both from genetic and epigenetic processes. In the current research, the effect of methyl-supplemented nutrition on the development of SLE was studied in the pristane-induced mouse model of the disease. The results clearly demonstrated decreased anti-dsDNA antibody and proteinuria levels, modulation of cytokines and protected renal structures in the group of treated mice. An additional increase in the DNA methylation of mouse B lymphocytes was also observed. The beneficial effect of the diet is due to the methyl-containing micronutrients with possible anti-inflammatory and immunomodulating effects on cell proliferation and gene expression. Since these components are responsible for maintaining the physiological methylation level of DNA, the results point to the central role of methylation processes in environmentally triggered lupus. As nutrition represents one of the major epigenetic factors, these micronutrients may be considered novel agents with significant therapeutic outcomes.
Assuntos
Anticorpos Antinucleares , Linfócitos B , Metilação de DNA , Suplementos Nutricionais , Modelos Animais de Doenças , Lúpus Eritematoso Sistêmico , Terpenos , Animais , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/induzido quimicamente , Camundongos , Anticorpos Antinucleares/imunologia , Anticorpos Antinucleares/sangue , Feminino , Linfócitos B/imunologia , Linfócitos B/metabolismo , Citocinas/metabolismo , Epigênese Genética , Micronutrientes/administração & dosagem , Proteinúria/imunologia , Rim/imunologia , Rim/metabolismo , Rim/patologia , Rim/efeitos dos fármacosRESUMO
Genetic susceptibility is necessary but not sufficient for systemic lupus erythematosus (SLE) to appear indicating that environmental factors are also key components in the disease onset. Aberrant DNA methylation profile positively correlates with the development of lupus-like disease in MRL/lpr mice. In the present study, we evaluate the effect of long term administration of methyl-rich diet in MRL mice. The results showed that supplemented diet decreased the levels of proteinuria and of anti-dsDNA antibodies and modulated cytokine profiles. Limited kidney failure and prevented development of skin lesions in MRL/lpr mice were another positive effects of the high-dose methyl diet. These data suggest that it is possible to modulate the disease course by altering the amount of particular dietary micronutrients and that nutrition-mediated changes in DNA methylation may have potential clinical relevance.