Publicações científicas

Interleukin-12 inhibits liver-specific drug-inducible systems in vivo

Reboredo M, Zabala M, Mauleon I, De Las Rivas J, Kreppel F, Kochanek S, Prieto J, Hernandez-Alcoceba R, Kramer MG.
Division of Hepatology and Gene Therapy, School of Medicine, Foundation for Applied Medical Research, University of Navarra, Pamplona, Navarra, Spain

Revisão:Gene Therapy

Data: 1/Fev/2008

Hepatologia

Drug-inducible systems allow modulation of the duration and intensity of cytokine expression in liver immuno-based gene therapy protocols. However, the biological activity of the transgene may influence their function.

We have analyzed the kinetics of interleukin-12 (IL-12) expression controlled by the doxycycline (Dox)- and the mifepristone (Mif)-dependent systems using two long-term expressing vectors directed to liver: a plasmid administered by hydrodynamic injection and a high-capacity adenoviral vector. Daily administration of Dox or Mif was associated with a progressive loss of inducibility and a decrease of murine IL-12 production. This inhibition occurred at the transcriptional level and was probably caused by an interferon (IFN)-gamma-mediated downmodulation of liver-specific promoters that control the expression of transactivators in these systems. Genome-wide expression microarrays studies revealed a parallel downregulation of liver-specific genes in mice overexpressing murine IL-12. However, a promoter naturally induced by IL-12 was also inhibited by this cytokine when placed in a plasmid vector. Interestingly, treatment with sodium butyrate, a class I/II histone deacetylase inhibitor, was able to rescue liver-specific promoter activity solely in the vector.

We conclude that biologically active IL-12 can transiently inhibit the function of drug-inducible systems in non-integrative DNA vectors by reducing promoter activity, probably through IFN-gamma and protein deacetylation-dependent mechanisms.

CITAÇÃO DO ARTIGO Gene Ther. 2008 Feb;15(4):277-88

talvezlhe interesse

QUE TECNOLOGIA UTILIZAMOS? 

A Clínica é o hospital privado com maiores recursos tecnológicos de Espanha, tudo num único centro.

Imagen de un PET, tecnología de vanguardia en la Clínica Universidad de Navarra

OS NOSSOS
PROFISSIONAIS

Os profissionais da Clínica realizam um trabalho contínuo de investigação e formação, sempre em benefício do paciente.

Imagen profesionales de la Clínica Universidad de Navarra

RAZÕES PARA VIR
À CLÍNICA

Conheça porque é que somos diferentes em relação a outros centros sanitários. Qualidade, rapidez, comodidade e resultados.

Imagen del edificio de la Clínica Universidad de Navarra