Estudo dos efeitos imuno moduladores de gangliosideos na inflamação/expressão do diabetes mellitus autoimune em camundongo Nod-Uni

AUTOR(ES)
DATA DE PUBLICAÇÃO

2005

RESUMO

The beta cells destruction on diabetes type 1 autoimmune knowledge was derivative from NOD (diabetic non obese) mouse as experimental model, which have demonstrated great potential for drugs or immunotherapy s study. In this model, the diabetes manifestation occurs spontaneously like the observed in human, among 128-248 week of life. The prevalence could be varied from 60-90% in females and 0-20% in males. The autoimmune mechanism study suggests the imbalance between Th1 and Th2 response with predominance Th1 phenotype (IL-1(3,TNF-a, IFN-y). Thus, it was necessary the study of the Th1 and Th2 cytokines related to autoimmunity of the diabetes in NOD mouse. Moreover, it believed that apoptosis of the beta cells it was associated with the diabetes manifestation in both human and experimental models. In such studies FaslFas-L were related with IL-1(3,IFN-y and TNF-a as effectors molecules of the cell death pancreatic islets. Gangliosides can block, in a selective manner, the pro-inflammatory (Th1) cytokines preduction like IFN-y and TNF-a and inhibit the T cells proliferation. However, these compounds can stimulate the synthesis of anti-inflammatory cytokines, like IL-4 and TGF- beta . In the present wOrk,we analyze the effect of the gangliosides (GM1,GD1a,GD1b, GT1b) treatment on diabetes mellitus manifestation in NOD mice. The glucose levels, injury index, CD4, CDa and CD11 immunohistochemical labeling, cytokines and apoptotic related molecules gene expression analyses and IL-12, IL-4, TGF- beta - TNF- alfa and IFN-y detection by immunoassay, were monitored. Our results showed that the ganglioside treatment frem 4th week of life prevents the on set of autoimmune diabetes, the inflammatory infiltrate installation. Th1 response can be suppresses by these compounds by the increase anti-inflammatory cytokines and the T cell apoptosis induction, besides the beta cells preservation. Therefore take together these results reinforce the immunomodulatory action of gangliosides treatment on the diabetes mellitus manifestation

ASSUNTO(S)

camundongos endogamicos nod gangliosideos doenças auto-imunes apoptose citocinas diabetes mellitus tipo 1

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