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PLoS One ; 10(11): e0142186, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26555789


CD26 is a T cell activation marker consisting in a type II transmembrane glycoprotein with dipeptidyl peptidase IV (DPPIV) activity in its extracellular domain. It has been described that DPPIV inhibition delays the onset of type 1 diabetes and reverses the disease in non-obese diabetic (NOD) mice. The aim of the present study was to assess the effect of MK626, a DPPIV inhibitor, in type 1 diabetes incidence and in T lymphocyte subsets at central and peripheral compartments. Pre-diabetic NOD mice were treated with MK626. Diabetes incidence, insulitis score, and phenotyping of T lymphocytes in the thymus, spleen and pancreatic lymph nodes were determined after 4 and 6 weeks of treatment, as well as alterations in the expression of genes encoding ß-cell autoantigens in the islets. The effect of MK626 was also assessed in two in vitro assays to determine proliferative and immunosuppressive effects. Results show that MK626 treatment reduces type 1 diabetes incidence and after 6 weeks of treatment reduces insulitis. No differences were observed in the percentage of T lymphocyte subsets from central and peripheral compartments between treated and control mice. MK626 increased the expression of CD26 in CD8+ T effector memory (TEM) from spleen and pancreatic lymph nodes and in CD8+ T cells from islet infiltration. CD8+TEM cells showed an increased proliferation rate and cytokine secretion in the presence of MK626. Moreover, the combination of CD8+ TEM cells and MK626 induces an immunosuppressive response. In conclusion, treatment with the DPPIV inhibitor MK626 prevents experimental type 1 diabetes in association to increase expression of CD26 in the CD8+ TEM lymphocyte subset. In vitro assays suggest an immunoregulatory role of CD8+ TEM cells that may be involved in the protection against autoimmunity to ß pancreatic islets associated to DPPIV inhibitor treatment.

Linfócitos T CD8-Positivos/efeitos dos fármacos , Diabetes Mellitus Tipo 1/prevenção & controle , Dipeptidil Peptidase 4/efeitos dos fármacos , Inibidores da Dipeptidil Peptidase IV/farmacologia , Fosfato de Sitagliptina/análogos & derivados , Animais , Autoantígenos/genética , Linfócitos T CD8-Positivos/imunologia , Diabetes Mellitus Tipo 1/imunologia , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos NOD , Fosfato de Sitagliptina/farmacologia , Fator de Crescimento Transformador beta/sangue
Virchows Arch ; 458(2): 141-51, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21240614


Dietary lipids have a role in the aetiology of breast cancer, acting at several cellular levels. We investigated the effects of a high corn oil and a high extra virgin olive oil diet on the clinical and histopathological characteristics of rat dimethylbenz(α)anthracene-induced mammary carcinogenesis and on the expression of p21Ha-Ras, detected by immunohistochemistry, in one experimental series including a low-fat corn oil diet (LFCO) and two high-fat diet groups: HFCO(P), rich in corn oil, and HFOO(P), rich in extra virgin olive oil. Whereas the high corn oil diet tended to reduce latency time, to raise tumour incidence and to increase total tumour yield, the high extra virgin olive oil diet led to a latency time similar to that of LFCO and to a lower tumour incidence than HFCO(P) and lower total tumour yield, even than LFCO. HFCO(P) tumours displayed a higher histological grade and profile than LFCO tumours, while adenocarcinomas in HFOO(P) were similar to LFCO ones. Although no significant differences in p21Ha-Ras expression among dietary groups was found, we detected a significant p21Ha-Ras decreasing expression as grade increased, in groups LFCO and HFCO(P). HFOO(P) tumours exhibited a higher staining in high-grade carcinomas compared to the similar malignant tumours of the two other dietary groups. These data suggest that dietary lipids influence the clinical behaviour and the morphological malignancy of the experimental mammary carcinogenesis, according to the type of fat, without altering p21Ha-Ras expression. Nevertheless, this expression could be affected by the malignancy of tumours, probably through a post-translational event.

Óleo de Milho/farmacologia , Dieta , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Óleos Vegetais/farmacologia , Proteínas Proto-Oncogênicas p21(ras)/biossíntese , Animais , Feminino , Imuno-Histoquímica , Azeite de Oliva , Ratos , Ratos Sprague-Dawley