Asunto(s)
Adenocarcinoma , Regulación Neoplásica de la Expresión Génica , Histamina/metabolismo , Neoplasias Mamarias Animales , Neovascularización Patológica , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Animales , Femenino , Histidina Descarboxilasa/genética , Histidina Descarboxilasa/metabolismo , Neoplasias Mamarias Animales/genética , Neoplasias Mamarias Animales/metabolismo , Neoplasias Mamarias Animales/patología , Ratones , Ratones NoqueadosRESUMEN
Interleukin-6 (IL-6) belongs to a family of cytokines that use receptors consisting of a common signal-transducing chain (gp130). Baf/3 cells transfected with the human IL-6 receptor (IL-6R) and gp130 (Baf/3-gp130/IL-6R) can only grow in medium containing IL-6. We attempted to interrupt the signal transducing pathway of IL-6 with the help of antisense oligonucleotides (ASOs) designed against the IL-6R. We used 18 different kinds of antisense oligonucleotides of overlapping sequences around the translational start codon of the human IL-6R. Sense ASOs were used as a control. The proliferation of cells was analysed by H-thymidine incorporation. Cell surface expression of the IL-6R was assessed by FACS analysis. We identified three ASOs which strongly inhibited the proliferation of IL-6 dependent transfected Baf/3 cells. Flow cytometric studies on the suppression of surface expression of IL-6R by ASOs showed a similar pattern. These results should help to clarify the structural requirements of functionally effective ASOs in the inhibition of IL-6R.
Asunto(s)
Interleucina-6/farmacología , Oligonucleótidos Antisentido/genética , Receptores de Interleucina-6/metabolismo , Transducción de Señal/efectos de los fármacos , Secuencia de Bases , División Celular/efectos de los fármacos , Línea Celular , Citometría de Flujo , Humanos , Oligonucleótidos Antisentido/farmacología , Receptores de Interleucina-6/biosíntesis , Receptores de Interleucina-6/deficiencia , Receptores de Interleucina-6/genética , Especificidad por Sustrato , Factores de TiempoRESUMEN
Growth hormone (GH), given therapeutically in many human diseases, is able to modulate the maturation and function of many cells of immune system. The present study demonstrates the effect of human recombinant GH on the production of acute phase proteins (APP) as well as on the gene expression of junB proto-oncogene on human hepatoma cell line, HepG2. When applied alone GH resulted in an increase in the transcription of junB proto-oncogene within 30 min. The production of alpha2-macroglobulin, haptoglobin and fibrinogen was also enhanced by rhGH treatment. However, both IL-6-stimulated junB gene expression (junB mRNA) and biosynthesis of type II APP (alpha2-macroglobulin, fibrinogen, haptoglobin) were strongly inhibited by the GH. The results indicate that GH has a modulatory role in regulating inflammation both in the absence and presence of IL-6. These findings call for further in vivo studies to determine the potential anti-inflammatory actions of GH therapy.