Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Más filtros










Base de datos
Intervalo de año de publicación
1.
Islets ; 3(5): 250-8, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21765243

RESUMEN

The search for factors either promoting islets proliferation or survival during adult life is a major issue for both type 1 and 2 diabetes mellitus. Among factors with mitogenic activity on pancreatic ß-cells, human placental lactogen (hPL) showed stronger activity when compared to the other lactogen hormones: growth hormone (GH) and prolactin (PRL). The aim of the present work is to elucidate the biological and molecular events of hPL isoform A (hPL-A) activity on human cultured islets. We used pure human pancreatic islets and insulinoma cell lines (ßTC-1 and RIN, murine and rat respectively) stimulated with hPL-A recombinant protein and we compared hPL-A activity with that of hGH. We showed that hPL-A inhibits apoptosis, both in insulinoma and human islets, by the phosphorylation of AKT protein. Indeed, the antiapoptotic role of hPL-A was mediated by PI3K, p38 and it was independent by PKA, Erk1/2. Compared with hGH, hPL-A modulated at different intervals and/or intensity by the phosphorylation of JAKs/STATs and MAPKinases. Moreover, hPL-A induced PDX-1 intracellular expression, improving beta cell activity and ameliorating insulin secretion in response to high glucose stimulation. Our data support the idea that hPL-A is involved in the regulation of beta cells activity. Importantly, we found that hPL-A can preserve and improve the ability of purified human pancreatic islets cultured to secrete insulin in vitro.


Asunto(s)
Células Secretoras de Insulina/citología , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Lactógeno Placentario/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Hormona de Crecimiento Humana/metabolismo , Hormona de Crecimiento Humana/farmacología , Humanos , Secreción de Insulina , Células Secretoras de Insulina/efectos de los fármacos , Insulinoma , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Neoplasias Pancreáticas , Lactógeno Placentario/farmacología , Prolactina/metabolismo , Prolactina/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
2.
J Immunol Methods ; 291(1-2): 153-63, 2004 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-15345313

RESUMEN

CD8+ T cell responses and particularly cytotoxic T lymphocyte (CTL) activity are critical factors in controlling SHIV, SIV or HIV replication during natural infection and represent key parameters which need to be monitored during vaccine development. In order to improve the methodology for measuring CD8+ T cell responses, retroviral vectors expressing the full-length SIV-Gag or HIV-Env proteins were constructed and used to transduce B lymphoblastoid cell lines (BLCL) from cynomolgus monkeys infected with SHIV89.6P. Continuous expression of Gag and Env proteins was detected in stably transduced BLCL, which induced Gag- or Env-specific T cell responses, as measured by both IFNgamma-ELISPOT and chromium release assays, upon in vitro stimulation of PBMC from the SHIV89.6P-infected monkeys. Moreover, induction of Gag-specific CTL using BLCL transduced with retroviral vector expressing the SIV-Gag protein was more efficient and specific compared to that obtained using BLCL infected with a recombinant vaccinia virus (rVV) encoding for the same antigen. Assays on purified CD4+ and CD8+ T cells indicated that both populations specifically produced IFNgamma, but only the CD8+ T cells mediated Gag- and Env-specific cytotoxicity, indicating preferential expansion of these effector cells. Thus, this method represents an alternative tool for the analysis of CTL responses during vaccination protocols in those animal models where little information is available on MHC class I alleles or CTL epitopes.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Vectores Genéticos/genética , VIH/genética , VIH/inmunología , Virus de la Inmunodeficiencia de los Simios/genética , Virus de la Inmunodeficiencia de los Simios/inmunología , Animales , Antígenos Virales/genética , Antígenos Virales/inmunología , Linfocitos T CD8-positivos/citología , División Celular , Células Cultivadas , Productos del Gen gag/genética , Productos del Gen gag/inmunología , Productos del Gen gag/metabolismo , Antígenos VIH/genética , Antígenos VIH/inmunología , Proteína gp120 de Envoltorio del VIH/genética , Proteína gp120 de Envoltorio del VIH/inmunología , Proteína gp120 de Envoltorio del VIH/metabolismo , Macaca fascicularis , Masculino , Sensibilidad y Especificidad , Linfocitos T Citotóxicos/citología , Linfocitos T Citotóxicos/inmunología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA