NF-kappa B activation is involved in regulation of cystic fibrosis transmembrane conductance regulator (CFTR) by interleukin-1 beta

• Autores: Cafferata, Eduardo; González Guerrico, Anatilde M.; Pivetta, Omar H.; Santa-Coloma, Tomás A.
• Año de publicación: 2001
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Journal of Biological Chemistry 2001;276(18):15441-15444
• Materia: Fibrosis Quística; Interleucina-1beta; Regulador de Conductancia de Transmembrana de Fibrosis Quística; Ensayo de Cambio de Movilidad Electroforética
• Institución: Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"

Fil: Cafferata, Eduardo. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica Dr. Eduardo Castilla. Departamento de Genética Experimental; Argentina.
Fil: González Guerrico, Anatilde M. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica Dr. Eduardo Castilla. Departamento de Genética Experimental; Argentina.
Fil: Pivetta, Omar H. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica Dr. Eduardo Castilla. Departamento de Genética Experimental; Argentina.
Fil: Santa-Coloma, Tomás A. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica Dr. Eduardo Castilla. Departamento de Genética Experimental; Argentina.
Interleukin-1 beta (IL-1 beta) regulates the levels of cystic fibrosis transmembrane conductance regulator (CFTR) mRNA and protein in the T84 human carcinoma cell line. Here, we studied the role of the transcription factor NF-kappaB in this regulation. Initially, T84 cells were pretreated with the NF-kappaB inhibitor pyrrolidine dithiocarbamate, Cells were then stimulated with IL-1 beta, and CFTR mRNA levels were determined after 4 h by Northern blot analysis. As a result of PDTC treatment, IL-1 beta stimulation of CFTR mRNA was blocked, On the other hand, daunorubicin, an NF-kappaB activator, increased the steady-state levels of CFTR mRNA, Furthermore, after treatment with IL-1 beta for 1 h, cytoplasmic I kappaB alpha degradation occurred simultaneously with translocation of p65 into the nucleus, The T84 cells were also transduced with an adenoviral vector expressing a dominant negative form of I kappaB alpha, which prevents I kappaB alpha phosphorylation and the subsequent nuclear translocation of NF-kappaB, After viral transduction, the cells were stimulated with IL-1 beta for 4 h, and CFTR mRNA levels were measured by Northern blot analysis. The stimulation of CFTR, induced by IL-1 beta, was also blocked in the presence of the dominant negative mutant. These results indicate that NF-kappaB is involved in the pathway by which IL-1 beta regulates CFTR.